Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

PubMed Central

Waters, Emily A; Chen, Junjie; Allen, John S; Zhang, Huiying; Lanza, Gregory M; Wickline, Samuel A

2008-01-01

Background Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of ανβ3 integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets. Methods New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with ανβ3 integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with ανβ3 integrin targeted PFC nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry. Results Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control animals. Nanoparticles were successfully detected in all samples scanned at 3.0T. PECAM endothelial staining and ανβ3 integrin staining revealed the presence of neovasculature within the valve leaflets. Conclusion Integrin-targeted PFC nanoparticles specifically detect early angiogenesis in sclerotic aortic valves of cholesterol fed rabbits. These techniques may be useful for assessing atherosclerotic components of preclinical aortic valve disease in patients and could assist in defining efficacy of medical therapies. PMID:18817557

Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate.

PubMed

Perségol, Laurence; Darabi, Maryam; Dauteuille, Carolane; Lhomme, Marie; Chantepie, Sandrine; Rye, Kerry-Anne; Therond, Patrice; Chapman, M John; Salvayre, Robert; Nègre-Salvayre, Anne; Lesnik, Philippe; Monier, Serge; Kontush, Anatol

2018-01-01

The functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether the vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. The capacity of five major HDL subfractions to counteract the inhibitory effects of oxidized LDL on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. NO production, an essential pathway in endothelium-dependent vasorelaxation, was studied in simian vacuolating virus 40-transformed murine endothelial cells (SVECs). Small dense HDL3 subfractions displayed potent vasorelaxing activity (up to +31% vs. baseline, P < 0.05); in contrast, large light HDL2 did not induce aortic-ring relaxation when compared on a total protein basis. HDL3 particles were enriched with sphingosine-1-phosphate (S1P) (up to 3-fold vs. HDL2), with the highest content in HDL3b and -3c that concomitantly revealed the strongest vasorelaxing properties. NO generation was enhanced by HDL3c in SVECs (1.5-fold, P < 0.01), a phenomenon that was blocked by the S1P receptor antagonist, VPC 23019. S1P-enriched reconstituted HDL (rHDL) was a 1.8-fold ( P < 0.01) more potent vasorelaxant than control rHDL in aortic rings. Small dense HDL3 particles displayed potent protective effects against oxidative stress-associated endothelium dysfunction, potentially reflecting their elevated content of S1P that might facilitate interaction with S1P receptors and ensuing NO generation. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

N,N-diacetyl-L-cystine improves endothelial function in atherosclerotic Watanabe heritable hyperlipidaemic rabbits.

PubMed

Pettersson, Knut S; Eliasson, Ulla Brandt; Abrahamsson, Tommy; Wågberg, Maria; Carrier, Martin; Kengatharan, Ken M

2007-01-01

N,N-diacetyl-L-cystine (DiNAC), a novel immunomodulator, stimulates contact sensitivity/delayed type hypersensitivity reactions in mice induced by oxazolone and reduces atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Forty-week-old WHHL rabbits were given DiNAC (3 micromol/kg per day) for 8 weeks, and endothelium-mediated dilatation was investigated in vivo using pulse wave analysis. A significant improvement in endothelial function was found after 3 weeks of treatment, which was further improved after 8 weeks. For experiments on isolated blood vessels, 40-week-old rabbits were treated for 3 weeks. Treatment did not affect plasma lipid levels. At termination, aortic rings from the thoracic and abdominal aorta were contracted with phenylephrine in vitro. Concentration-effect curves to acetylcholine and the calcium ionophore A 23187 were used to measure endothelium-mediated vasodilatation, and nitroprusside to elicit endothelium-independent relaxations. Abdominal aorta relaxations were generally larger than in thoracic aorta. DiNAC improved endothelium-dependent relaxations in the abdominal but not in the thoracic aorta. This effect was independent of the degree of atherosclerosis. It is concluded that DiNAC improved endothelial function in atherosclerotic rabbit arteries in vivo and in vitro, and may represent a new treatment modality for atherosclerosis-related diseases.

Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits.

PubMed

Shehatou, George S G; Suddek, Ghada M

2016-02-01

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. © 2016 by the Society for Experimental Biology and Medicine.

Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits

PubMed Central

Suddek, Ghada M

2016-01-01

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. PMID:26490346

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model.

PubMed

El-Hawli, Aisha; Qaradakhi, Tawar; Hayes, Alan; Rybalka, Emma; Smith, Renee; Caprnda, Martin; Opatrilova, Radka; Gazdikova, Katarina; Benckova, Maria; Kruzliak, Peter; Zulli, Anthony

2017-02-01

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

PubMed

Qamar, Hafiz Misbah-Ud-Din; Qayyum, Rahila; Salma, Umme; Khan, Shamim; Khan, Taous; Shah, Abdul Jabbar

2018-12-01

Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

The role of annular dimension and annuloplasty in tricuspid aortic valve repair.

PubMed

de Kerchove, Laurent; Mastrobuoni, Stefano; Boodhwani, Munir; Astarci, Parla; Rubay, Jean; Poncelet, Alain; Vanoverschelde, Jean-Louis; Noirhomme, Philippe; El Khoury, Gebrine

2016-02-01

Valve sparing reimplantation can improve the durability of bicuspid aortic valve repair compared with subcommissural annuloplasty, especially in patients with a large basal ring. This study analyses the effect of basal ring size and annuloplasty on valve repair in the setting of a tricuspid aortic valve. From 1995 to 2013, 382 patients underwent elective tricuspid aortic valve repair. We included only those undergoing subcommissural annuloplasty, valve sparing reimplantation or no annuloplasty and in whom intraoperative transoesophageal echocardiography images were available for retrospective pre- and post-repair basal ring measurements (n = 323, subcommissural annuloplasty: 146, valve sparing reimplantation: 154, no annuloplasty: 23). In a subgroup of patients with available echocardiographic images, basal ring was retrospectively measured at the latest follow-up or prior to reoperation. subcommissural annuloplasty and valve sparing reimplantation were compared after matching for degree of aortic regurgitation and root size. All three groups differed significantly for most of preoperative characteristics. Hospital mortality was 0.9%. The median follow-up was 4.7 years. At 8 years, overall survival was 80 ± 5%. Freedom from reoperation and freedom from aortic regurgitation >1+ were 92 ± 5% and 71 ± 8%, respectively. In multivariate analysis, predictors of aortic regurgitation >1+ were left ventricular end-diastolic diameter (P = 0.003), cusp repair (P = 0.006), body surface area (P = 0.01) and subcommissural annuloplasty (P = 0.05). In subcommissural annuloplasty, freedom from aortic regurgitation >1+ was lower for patients with basal ring ≥28 mm compared with patients with basal ring <28 mm (P = 0.0001). In valve sparing reimplantation, freedom from aortic regurgitation >1+ was independent of basal ring size (P = 0.38). In matched comparison between subcommissural annuloplasty and valve sparing reimplantation, freedom from aortic regurgitation >1+ was not significantly different (P = 0.06), but in patients with basal ring ≥28 mm, valve sparing reimplantation was superior to subcommissural annuloplasty (P = 0.04). Despite similar intraoperative reduction in basal ring size in subcommissural annuloplasty and valve sparing reimplantation, patients with subcommissural annuloplasty exhibited greater increase in basal ring size during the follow-up compared with the valve sparing reimplantation group (P < 0.001). As with a bicuspid aortic valve, a large basal ring predicts recurrence of aortic regurgitation in patients with tricuspid aortic valve undergoing repair with the subcommissural annuloplasty technique. This recurrence is caused by basal ring dilatation over time after subcommissural annuloplasty. With the valve sparing reimplantation technique, large basal ring did not predict aortic regurgitation recurrence, as prosthetic-based circumferential annuloplasty displayed better stability over time. Stable circumferential annuloplasty is recommended in tricuspid aortic valve repair whenever the basal ring size is ≥28 mm. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Biphasic effect of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract on rat isolated vascular smooth muscles.

PubMed

Chiwororo, Witness D H; Ojewole, John A O

2008-12-01

In this study, we examined the effects of Psidium guajava Linn. leaf aqueous extract (PGE) on isolated, spontaneously-contracting portal veins, as well as on endothelium-intact and endothelium-denuded descending thoracic aortic ring preparations of healthy, normotensive rats. Graded concentrations of PGE (0.25-4.0 mg/ml) caused concentration-dependent, initial brief but significant (P<0.05) rises of the basal tones and amplitudes of pendular, rhythmic contractions, followed by secondary pronounced, longer-lasting and significant (P<0.05-0.001) inhibitions of contractile amplitudes of the isolated portal veins. Relatively low concentrations of PGE (<1.0 mg/ml) always contracted freshly-mounted, naïve, endothelium-intact aortic ring preparations. However, relatively high concentrations of PGE (1.0-4.0 mg/ml) always produced initial brief contractions/augmentations of noradrenaline (NA, 10(-7)M)-induced contractions of endothelium-intact and endothelium-denuded aortic ring preparations, followed by secondary, pronounced relaxations of the aortic ring muscles. Moreover, relatively high concentrations of PGE (1.0-4.0 mg/kg) always relaxed NA-induced contractions of the aortic ring preparations in a concentration-related manner. The arterial-relaxing effects of PGE were more pronounced in endothelium-intact aortic rings than in endothelium-denuded aortic ring preparations. The relaxant effects of PGE on endothelium-intact aortic rings were only partially inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), a nitric oxide synthase inhibitor, suggesting that the vasorelaxant effect of PGE on aortic rings is probably mediated via both endothelium-derived relaxing factor (EDRF)-dependent and EDRF-independent mechanisms. Taken together, the findings of this study indicate that PGE possesses a biphasic effect on rat isolated vascular smooth muscles.

Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine.

PubMed

Kurahashi, K; Shibata, S

1971-09-01

1. Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine.2. Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine.3. Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine.4. Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5-hydroxytryptamine (5-HT).5. The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants.

Anti-fibrin antibody binding in valvular vegetations and kidney lesions during experimental endocarditis.

PubMed

Yokota, M; Basi, D L; Herzberg, M C; Meyer, M W

2001-01-01

In Streptococcus sanguinis (sanguis) induced experimental endocarditis, we sought evidence that the development of aortic valvular vegetation depends on the availability of fibrin. Endocarditis was induced in New Zealand white rabbits by catheter placement into the left ventricle and inoculation of the bacteria. Fibrin was localized in the developing vegetation with 99mTechnetium (Tc)-labeled anti-fibrin antibody one or three days later. When rabbit anti-fibrin antibody was given intravenously on day 1, the mass of aortic valvular vegetation was significantly reduced at day 3; infusion of non-specific rabbit IgG showed no effect. The 99mTc-labeled anti-fibrin antibody also labeled kidneys that showed macroscopic subcapsular hemorrhage. To learn if the deposition of fibrin in the kidneys was a consequence of endocarditis required a comparison of farm-bred and specific pathogen-free rabbits before and after the induction of endocarditis. Before induction, the kidneys of farm-bred rabbits were labeled, but specific pathogen-free rabbits were free of labeling and signs of macroscopic hemorrhage. After 3 days of endocarditis, kidneys of 10 of 14 specific pathogen-free rabbits labeled with 99mTc-labeled anti-fibrin antibody and showed hemorrhage. Kidney lesions were suggested to be a frequent sequellae of S. sanguinis infective endocarditis. For the first time, fibrin was shown to be required for the continued development of aortic valvular vegetations.

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

PubMed

El-Sheakh, Ahmed R; Ghoneim, Hamdy A; Suddek, Ghada M; Ammar, El-Sayed M

2015-12-01

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20 mg/kg/day), or HCD plus atorvastatin (10 mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that flavocoxid would be useful in preventing oxidative stress, inflammation, and vascular dysfunction induced by HCD.

Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine

PubMed Central

Kurahashi, K.; Shibata, S.

1971-01-01

1. Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine. 2. Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine. 3. Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine. 4. Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5-hydroxytryptamine (5-HT). 5. The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants. PMID:4400183

Patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement. Experimental study.

PubMed

Manouguian, S; Abu-Aishah, N; Neitzel, J

1979-09-01

The experimental results of patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement are reported. The operative technique of this new surgical method is described and the indications are discussed.

Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced Hypercholesterolemic rabbits.

PubMed

Ibrahim, Muhammad; Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ishola, Afeez Adekunle; Draman, Samsul; Isa, Muhammad Lokman Md; Yusof, Afzan Mat

2017-07-07

Atherosclerosis is the most common disease of large and medium-sized arteries linked to oxidative stress, dyslipidemia as well as chronic inflammation. The aim of this study was to evaluate the potential health benefits of Baccaurea angulata (BA) fruit juice on the aorta of diet-induced hypercholesterolemic rabbits, to detect an accumulation of fatty streak and evaluate the percentage of atherosclerotic lesion accrued. Thirty-five healthy male adults New Zealand White rabbits were assigned to seven different groups. Four groups were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL of BA fruit juice per kg of rabbit daily (atherogenic groups), while the other three groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg of rabbit daily (normocholesterolemic groups) for 90 days. The thoracic and abdominal aorta between the heart origin and bifurcation into iliac arteries of all the rabbits were carefully removed and analyzed accordingly. The supplementation of the high-cholesterol diet of hypercholesterolemic rabbits with only 0.5 mL BA/kg rabbit per day significantly (p < 0.001) improved aortic lipid profile, attenuated aortic fatty streak development and reduced intima thickening. Higher BA doses used (1.0 and 1.5 mL/kg rabbit per day) also significantly (p < 0.001) decreased further the development of aortic fatty streaks, reduced the thickening of the tunica intima layer and preserved endothelial healing following arterial injury. Therefore, BA fruit is a potential novel functional food with effective anti-inflammatory, anti-atherogenic and hypocholesterolemic activities.

Effect of melatonin on vascular responses in aortic rings of aging rats.

PubMed

Reyes-Toso, Carlos F; Obaya-Naredo, Daniel; Ricci, Conrado R; Planells, Fernando M; Pinto, Jorge E; Linares, Laura M; Cardinali, Daniel P

2007-04-01

In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10(-5)mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 m mol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits.

PubMed

Hadi, Najah R; Al-Amran, Fadhil; Hussein, Mohammad A A; Rezeg, Fadhil A

2012-01-01

Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin - 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

Effects of Lycopene on the Initial State of Atherosclerosis in New Zealand White (NZW) Rabbits

PubMed Central

Lorenz, Mario; Fechner, Mandy; Kalkowski, Janine; Fröhlich, Kati; Trautmann, Anne; Böhm, Volker; Liebisch, Gerhard; Lehneis, Stefan; Schmitz, Gerd; Ludwig, Antje; Baumann, Gert; Stangl, Karl; Stangl, Verena

2012-01-01

Background Lycopene is the main carotenoid in tomatoes, where it is found in high concentrations. Strong epidemiological evidence suggests that lycopene may provide protection against cardiovascular diseases. We therefore studied the effects of lycopene on diet-induced increase in serum lipid levels and the initiation of atherosclerosis in New Zealand White (NZW) rabbits. Methodology/Principal Findings The animals, divided into four groups of 9 animals each, were fed either a standard diet, a high-cholesterol diet containing 0.5% cholesterol, a high-cholesterol diet containing placebo beadlets, or a high-cholesterol diet plus 5 mg/kg body weight/day of lycopene (in the form of lycopene beadlets), for a period of 4 weeks. We found significantly elevated lycopene plasma levels in the animal group treated with lycopene beadlets. Compared to the high-cholesterol and the placebo group, this was associated with a significant reduction of 50% in total cholesterol and LDL cholesterol serum levels in the lycopene group. The amount of cholesteryl ester in the aorta was significantly decreased by lycopene. However, we did not observe a significant decrease in the extent of aortic surface lipid accumulation in the lycopene group. In addition, no differences in the intima-media thickness among groups were observed. Endothelial-dependent and endothelial-independent vasodilation in isolated rabbit aortic and carotid rings did not differ among any of the animal groups. Conclusions Lycopene supplementation for 4 weeks increased lycopene plasma levels in the animals. Although we found strongly reduced total and LDL cholesterol serum levels as well as significantly lower amounts of cholesteryl ester in the aortae in the lycopene-treated group, no significant differences in initial lesions in the aortae were detected. PMID:22295112

Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta.

PubMed

Edirisinghe, Indika; McCormick Hallam, Kellie; Kappagoda, C Tissa

2006-08-01

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose-response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA-albumin complexes derived from lauric (C(12:0)), myristic (C(14:0)), palmitic (C(16:0)), stearic (C(18:0)) and linolenic (C(18:3)) acids. EDR induced by acetylcholine (0.1-10 mumol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5-2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.

Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

PubMed

Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

2011-02-01

Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

The aortic ring model of angiogenesis: a quarter century of search and discovery

PubMed Central

Nicosia, R F

2009-01-01

The aortic ring model has become one of the most widely used methods to study angiogenesis and its mechanisms. Many factors have contributed to its popularity including reproducibility, cost effectiveness, ease of use and good correlation with in vivo studies. In this system aortic rings embedded in biomatrix gels and cultured under chemically defined conditions generate arborizing vascular outgrowths which can be stimulated or inhibited with angiogenic regulators. Originally based on the rat aorta, the aortic ring model was later adapted to the mouse for the evaluation of specific molecular alterations in genetically modified animals. Viral transduction of the aortic rings has enabled investigators to overexpress genes of interest in the aortic cultures. Experiments on angiogenic mechanisms have demonstrated that formation of neovessels in aortic cultures is regulated by macrophages, pericytes and fibroblasts through a complex molecular cascade involving growth factors, inflammatory cytokines, axonal guidance cues, extracellular matrix (ECM) molecules and matrix-degrading proteolytic enzymes. These studies have shown that endothelial sprouting can be effectively blocked by depleting the aortic explants of macrophages or by interfering with the angiogenic cascade at multiple levels including growth factor signalling, cell adhesion and proteolytic degradation of the ECM. In this paper, we review the literature in this field and retrace the journey from our first morphological descriptions of the aortic outgrowths to the latest breakthroughs in the cellular and molecular regulation of aortic vessel growth and regression. PMID:19725916

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

PubMed

Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

2009-11-01

The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging. Georg Thieme Verlag KG Stuttgart, New York.

Targeting the Nociceptin/Orphanin FQ Receptor for Scleroderma Therapy

DTIC Science & Technology

2015-12-01

bottom well; the number of migrating cells is quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will...quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small-vessel myograph. KO

Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.

PubMed

Mo, Jiao; Yang, Renhua; Li, Fan; Zhang, Xiaochao; He, Bo; Zhang, Yue; Chen, Peng; Shen, Zhiqiang

2018-03-15

Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats. Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H 2 O 2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD). Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H 2 O 2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin. Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the clinical use of scutellarin in cardiovascular diseases. Copyright © 2018 Elsevier GmbH. All rights reserved.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

PubMed Central

Hadi, Najah R.; Al-Amran, Fadhil; Hussein, Mohammad A. A.; Rezeg, Fadhil A.

2012-01-01

Background: Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. Objectives: The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Materials and Methods: Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin – 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Results: Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Conclusions: Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters. PMID:22346138

Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yi-Xiang J., E-mail: yi-xiang.wang@astrazeneca.com; Kuribayashi, Hideto; Wagberg, Maria

Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killedmore » for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of age (p < 0.001). There was a small increase in aortic wall thickness between 50 and 73 weeks of age, but this was not significant (p > 0.05). The corresponding differences in lumen cross-sectional areas at 20, 50, and 73 weeks of age were not significant. These results were consistent with in-house historical histology data on this strain of rabbits. Conclusions. High-resolution gradient echo MRI can follow disease progression in the WHHL rabbit spontaneous atherosclerosis disease model.« less

The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit

PubMed Central

Alissa, Eman M; Bahijri, Suhad M; Lamb, David J; Ferns, Gordon A A

2004-01-01

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25–1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination. PMID:15379959

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

PubMed Central

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

PubMed

Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

2010-08-01

Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

PubMed

Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2012-02-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9

PubMed Central

Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2013-01-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis. PMID:22042083

Vasorelaxant effect of the analgesic clonixin on rat aorta.

PubMed

Morales, M A; Silva, A; Brito, G; Bustamante, S; Ponce, H; Paeile, C

1995-03-01

1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2. Clx completely relaxed aortic rings contracted by KCl 70 mM and together with its analog flunixin exhibited lesser potency but equal efficacy than verapamil. In comparison, indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about 40% of the maximal contraction of aortic rings. 3. Furthermore, Clx antagonized Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction suggesting its calcium antagonist character. 4. From these results it can be concluded that the hypotensive effect seen in rats in vivo after Clx i.v. injection arises because of vasodilatory effect of Clx and gives further support to the proposal that the pharmacological mechanism of action of Clx should be calcium antagonism.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet.

PubMed

Hsu, Howard H T; Culley, Nathan C

2006-06-23

Vascular calcification is implicated in myocardial infarction, instability and rigidity of the aortic wall, and bioprosthetic failures. Although an increase in the calcium (Ca) content in atherogenic diets has been shown to decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency can affect atherosclerosis-related aortic calcification remains unknown. New Zealand White male rabbit littermates were fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were dissected from rabbits for histological evaluations and Ca and Pi determinations. Rabbits with calcium supplementation were maintained for 4 months, whereas those with calcium deficiency were maintained for 2 1/2 months due to severe icterus beyond this stage. The ratios of intimal to medial areas and calcified to intimal areas were used to semi-quantify lesion accumulation and calcification, respectively. Icterus was estimated from the extent of yellowing of the skin, sclera, and mucous membranes along with gross evidence of hepatic lipidosis and/or biliary obstructions. Statistical analysis of 16 matched littermates shows that Ca supplementation significantly decreased the lesions by 41% (p < 0.05) and markedly inhibited calcification by 62% (p < 0.05). Statistical analysis of 11 matched littermates shows that Ca deficiency significantly increased the lesions by 2.7-fold (p < 0.05) and that the diet caused a small but significant calcification not seen in the sibling groups with normal dietary Ca. Ca supplementation caused a significant 30% decrease in serum cholesterol (p < 0.05). Calcium deficiency increased serum cholesterol by 57% (p < 0.001). Serum cholesterol and LDL-cholesterol levels in Ca deficient rabbits were 2-fold higher than those with high Ca diets. Ca supplementation decreased soluble Ca and Pi content in aortas, suggesting that this effect may underlie the effects of Ca supplementation on calcification. Calcium deficiency increased icterus by 33% (p < 0.05), which may affect hepatic clearance of cholesterol, while calcium supplementation decreased it by 43% (p < 0.001). Ca supplementation to an atherogenic diet inhibits atherosclerosis, aortic calcification, and icterus, whereas a Ca deficient-diet promotes them.

Suppression of atherosclerotic changes in cholesterol-fed rabbits treated with an oral inhibitor of neutral endopeptidase 24.11 (EC 3.4.24.11).

PubMed

Kugiyama, K; Sugiyama, S; Matsumura, T; Ohta, Y; Doi, H; Yasue, H

1996-08-01

Neutral endopeptidase 24.11 (NEP), widely distributed in the body, hydrolyzes and inactivates a number of endogenous vasoactive peptides, some of which could alter various functions of cells present in the arterial wall. Recently NEP has been found to exist in the vascular endothelium. The aim of this study was to assess the influence of chronic NEP inhibition by daily administration of UK79300 (candoxatril), an orally active NEP inhibitor (NEPI), on the development of atherosclerotic changes in high-cholesterol-fed rabbits. Male New Zealand White rabbits were fed for 8 weeks as follows: normal rabbit diet (Normal, n = 15), 1.5% cholesterol diet (Cholesterol, n = 15), or 1.5% cholesterol diet containing NEPI (20 mg.kg-1.d-1) (Cholesterol+NEPI, n = 15). At the end of the dietary period, NEPI treatment was found to suppress the surface area of the aorta covered by plaques (% surface area: Cholesterol, 59 +/- 6 versus Cholesterol+NEPI, 36 +/- 7, P < .01) and decreased contents of cholesterol and cholesterol esters in the aortas. NEPI also reduced plasma total cholesterol by 27% of Cholesterol rabbits (1781 +/- 130 mg/dL). The endothelial function, estimated by the endothelium-dependent relaxation of the isolated aortas in response to acetylcholine, was preserved in Cholesterol+NEPI rabbits compared with that in Cholesterol rabbits. NEP enzymatic activities in plasma and the particulate fraction of the homogenates from the aortas in Cholesterol rabbits were both increased, 3.1- and 3.9-fold, respectively, above those in Normal rabbits, but the activities in Cholesterol+NEPI rabbits were significantly lower than those in Cholesterol rabbits. UK73967, an active form of UK79300, or phosphoramidon partly reversed the atherosclerotic impairment of relaxation of the isolated thoracic aortic rings from Cholesterol rabbits in response to exogenous additions of C-type natriuretic peptide (CNP) and substance P, which are NEP substrates known to exist endogenously in the vascular endothelium. The results suggest that the increased NEP activity plays a significant role in atherogenesis, and NEPIs might be therapeutically useful in the prevention of atherosclerosis. Reduction of plasma cholesterol and suppression of degradations in the arteries of endogenously released CNP, substance P, or possibly other kinins known to have anti-atherosclerotic actions may at least partially contribute to the inhibitory effects of NEPIs on atherosclerotic changes.

Effect of aspirin on the contractility of aortic smooth muscle and the course of blood pressure development in male spontaneously hypertensive rats.

PubMed

Rahmani, M A; David, V; Huang, M; DeGray, G

1998-01-01

The effects of acetylsalicylic acid (ASA) on aortic smooth muscle contractility were studied in aortic rings of male SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for ten weeks. Blood pressure of each rat was monitored twice weekly prior to the i.p. injections. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, Phenylephrine (PE), Clonidine and Norepinephrine (NE). In another set of experiments calcium conductance was evaluated in the presence or absence of endothelium both in ASA treated and non treated animals. We report that aortic rings from ASA-treated SHR animals were more responsive to contractile agents than rings from non-treated SHR male rats. Also, the Ca2+ conductance in vitro was enhanced appreciably in SHR aortic rings denuded of their monolayer of endothelium in response to ASA treatment. No decrease in systolic blood pressure was observed in response to ASA treatment in SHR male rats. These results suggest that acetylsalicylic acid not only may modulate aortic smooth muscle contractility through the metabolites of arachidonic acid but may repair to a great extent the hypertension associated plasma membrane permeability defect of vascular myocytes.

Antispasmodic, bronchodilator, vasorelaxant and cardiosuppressant effects of Buxus papillosa.

PubMed

Khan, Arif-Ullah; Ali, Shamsher; Gilani, Anwarul-Hassan; Ahmed, Manzoor; Choudhary, Muhammad Iqbal

2017-01-18

The present research was carried out to investigate pharmacological properties of Buxus papillosa C.K. Schneid. (Buxaceae). Buxus papillosa extracts of leaves (BpL), stem (BpS), roots (BpR) and BpL fractions: hexane (BpL-H), aqueous (BpL-A) also plant constituent, cyclomicrobuxine effect were studied in jejunum, atria, aorta and tracheal preparations from rabbit and guine-peg. Ca ++ antagonistic effect of BpS, BpR, BpL-H, BpL-A and cyclomicrobuxine were conclusively suggested, when spontaneous contractions of rabbit jejunal preparation was relaxed along with subsequent relaxation of potassium chloride (80 mM) induced contractions. Ca ++ antagonistic effect was further confirmed, when a prominent right shift like that of verapamil was observed in Ca ++ concentration-response curves, drawn in a tissue pretreated with BpL (0.3-1.0 mg/mL). In rabbit tracheal tissues BpL, BpS, BpR, BpL-H and BpL-A produced a prominent relaxation in contractions induced by potassium chloride (80 mM) and carbachol (1 μm). When tested in rabbit aortic rings, BpL, BpS, BpR, BpL-H and BpL-A showed concentration-dependent (0.1-3.0 mg/mL) vasorelaxant effect against phenylephrine (1 μM) and high K + -induced contractions. In isolated guinea-pig right atria, BpL, BpS, BpR, BpL-H and BpL-A suppressed atrial force of spontaneous contractions, with BpL-A being most potent. Our results reveal that Buxus papillosa possesses gut, airways and cardiovascular inhibitory actions.

Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein.

PubMed

Ngo, Doan T M; Stafford, Irene; Kelly, Darren J; Sverdlov, Aaron L; Wuttke, Ronald D; Weedon, Helen; Nightingale, Angus K; Rosenkranz, Anke C; Smith, Malcolm D; Chirkov, Yuliy Y; Kennedy, Jennifer A; Horowitz, John D

2008-08-20

Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, P<0.0001), increased transvalvular velocity and transvalvular pressure gradient (both P<0.01 via 2-way ANOVA) compared to the control group. There was associated valve calcification, lipid deposition and macrophage infiltration. Endothelial function was markedly impaired, and intravalvular TXNIP concentration increased. In this model, vitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.

Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

PubMed

Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

2016-04-01

To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

Abdominal aortic aneurysm neck remodeling after Anaconda stent graft implantation.

PubMed

Vukovic, Elisabeth; Czerny, Martin; Beyersdorf, Friedhelm; Wolkewitz, Martin; Berezowski, Mikolaj; Siepe, Matthias; Blanke, Philipp; Rylski, Bartosz

2018-05-24

The aim of this study was to define how the proximal landing zone changes geometrically after endovascular abdominal aortic aneurysm repair (EVAR) with the Anaconda (Vascutek, Inchinnan, United Kingdom) stent graft. Among 230 patients who underwent Anaconda stent graft implantation between 2005 and 2014, we included 126 with adequate computed tomography (CT) image quality and follow-up. CT analysis entailed the geometric changes in the main body, proximal rings, and proximal landing zone. The median CT follow-up was 2.0 years (345.8 patients-years). The proximal portion of the main body ring system flattened within the first year after EVAR, resulting in an up to 30° increase in the upper ring's angle in 40% patients and up to 40° increase in 24% patients. One year after EVAR, the upper ring angle increase slowed down. Aortic diameter measured at the level of the upper and lower ring expanded by 2 to 4 mm within 1 year, but remained unchanged afterward. The main body migrated continuously down toward the aortic bifurcation, attaining an average 6-mm increase in the distance between the superior mesenteric artery and main body within 4 years. Freedom from endoleak type IA was 95 ± 2% and 93 ± 3% after 1 and 4 years, respectively. The Anaconda main body ring system in its proximal portion flattens within the first year after EVAR, leading to an increase of 2 to 4 mm in the proximal landing zone's aortic diameter. The main body migrates slowly but continuously down toward the aortic bifurcation. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings

PubMed Central

Yan, Yu; Chen, Yu-cai; Lin, Yi-huang; Guo, Jing; Niu, Zi-ran; Li, Li; Wang, Shou-bao; Fang, Lian-hua; Du, Guan-hua

2015-01-01

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay. Results: Application of brazilin (10–100 μmol/L) dose-dependently relaxed the NE- or high K+-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K+-induced extracellular Ca2+ influx and NE-induced intracellular Ca2+ release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca2+ channels. PMID:26564314

High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: mechanisms involved.

PubMed

Alarcon, Gabriela; Roco, Julieta; Medina, Mirta; Medina, Analia; Peral, Maria; Jerez, Susana

2018-01-30

Obesity contributes significantly to the development and evolution of cardiovascular disease (CVD) which is believed to be mediated by oxidative stress, inflammation and endothelial dysfunction. However, the vascular health of metabolically obese and normal weight (MONW) individuals is not completely comprehended. The purpose of our study was to evaluate vascular function on the basis of a high fat diet (HFD)-MONW rabbit model. Twenty four male rabbits were randomly assigned to receive either a regular diet (CD, n = 12) or a high-fat diet (18% extra fat on the regular diet, HFD, n = 12) for 6 weeks. Body weight, TBARS and gluthathione serum levels were similar between the groups; fasting glucose, triglycerides, C reactive protein (CRP), visceral adipose tissue (VAT), triglyceride-glucose index (TyG index) were higher in the HFD group. Compared to CD, the HFD rabbits had glucose intolerance and lower HDL-cholesterol and plasma nitrites levels. Thoracic aortic rings from HFD rabbits exhibited: (a) a reduced acetylcholine-induced vasorelaxation; (b) a greater contractile response to norepinephrine and KCl; (c) an improved angiotensin II-sensibility. The HFD-effect on acetylcholine-response was reversed by the cyclooxygenase-2 (COX-2) inhibitor (NS398) and the cyclooxygenase-1 inhibitor (SC560), and the HFD-effect on angiotensin II was reversed by NS398 and the TP receptor blocker (SQ29538). Immunohistochemistry and western blot studies showed COX-2 expression only in arteries from HFD rabbits. Our study shows a positive pro-inflammatory status of HFD-induced MONW characterized by raised COX-2 expression, increase of the CRP levels, reduction of NO release and oxidative stress-controlled conditions in an early stage of metabolic alterations characteristic of metabolic syndrome. Endothelial dysfunction and increased vascular reactivity in MONW individuals may be biomarkers of early vascular injury. Therefore, the metabolic changes induced by HFD even in normal weight individuals may be associated to functional alterations of blood vessels.

Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria-style diet

PubMed Central

López-Canales, Jorge Skiold; Lozano-Cuenca, Jair; López-Canales, Oscar Alberto; Aguilar-Carrasco, José Carlos; Aranda-Zepeda, Lidia; López-Sánchez, Pedro; Castillo-Henkel, Enrique Fernando; López-Mayorga, Ruth Mery; Valencia-Hernández, Ignacio

2015-01-01

The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10−9–10−5-mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10−5-mol/L NG-nitro-l-arginine methyl ester, 10−2-mol/L tetraethylammonium, 10−3-mol/L 4-aminopyridine, 10−7-mol/L apamin plus 10−7-mol/L charybdotoxin, 10−5-mol/L indomethacin, or 10−5-mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca2+-activated and voltage-activated K+ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect. PMID:25881486

Effect of agmatine on experimental vascular endothelial dysfunction.

PubMed

Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

2016-05-01

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

The effects of magnesium sulphate and EDTA in the hypercholesterolaemic rabbit.

PubMed

Evans, D A; Tariq, M; Sujata, B; McCann, G; Sobki, S

2001-12-01

Numerous clinical reports suggest the beneficial effects of chelation therapy for the treatment of atherosclerosis. However, the results of these studies are inconclusive and controversial. The purpose of this present study was to examine the prophylactic and therapeutic effects of chelation liquid (CHL) in experimental atherosclerosis. Twenty New Zealand white rabbits were fed a 1% cholesterol-supplemented diet for 45 days. In the prophylactic phase of the study subcutaneous 300 mg EDTA + 500 mg magnesium sulphate (MgSO4) injections (five rabbits) and isotonic saline (five rabbits) were given to test and control groups, respectively, along with cholesterol rich diet. The CHL treatment ameliorated the rise of serum cholesterol and serum triglyceride concentrations, lowered serum calcium concentrations and reduced the aortic atheroma. In the therapeutic phase of the experiment the cholesterol diet was stopped and the remaining 10 animals were returned to normal diet. Five of these rabbits were given CHL injections and other five animals were given isotonic saline injections for 121 days. Although the level of cholesterol and triglyceride were not significantly different in the two groups, the serum calcium concentration and the percentage of the area of flate aortic specimen occupied by atheroma were significantly lower in the CHL treated rabbits as compared to controls. It is concluded that CHL injections have a definite prophylactic effect on atherogenesis in the cholesterol-fed rabbit, and may have some therapeutic value in the regression phase. Further confirmatory studies are suggested.

Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits

PubMed Central

Castelo-Branco, Camil; Sanjuán, Alex; Ascaso, Carles; Colodrón, Marta; Blümel, Juan Enrique; Casals, Elena; Ordi, Jaume; Vanrell, Juan Antonio

2003-01-01

BACKGROUND: Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known. OBJECTIVE: To investigate the effect of tibolone therapy on aorta atherogenesis. MATERIAL AND METHODS: Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S). RESULTS: After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17±0.72 mmol/L to 35.36±9.01 mmol/L, in group S from 2.88±0.9 mmol/L to 28.76±9.442 mmol/L, in group E from 1.69±0.44 mmol/L to 1.69±0.44 mmol/L and in group T from 2.03±0.22 mmol/L to 26.33±13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47±12.2%, 24.51±16.1%, 17.91±10.19% and 10.21±6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups). CONCLUSION: The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels. PMID:19644583

Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits.

PubMed

Yamakoshi, J; Kataoka, S; Koga, T; Ariga, T

1999-01-01

The aim of this study was to evaluate the antiatherosclerotic effect of proanthocyanidin-rich extracts from grape seeds in cholesterol-fed rabbits. Proanthocyanidin-rich extracts (0.1% and 1% in diets [w/w]) did not appreciably affect the changes in serum lipid profile of cholesterol-fed rabbits. The level of cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2'-azobis(2-amidinopropane-dihydrochloride (AAPH) were lower in the plasma of rabbits fed proanthocyanidin-rich extract plus cholesterol than in the plasma of rabbits fed cholesterol alone, but not in the low-density lipoprotein (LDL). Aortic malondialdehyde (MDA) content decreased in rabbits fed proanthocyanidin-rich extract. Feeding proanthocyanidin-rich extracts (0.1 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Immunohistochemical analysis revealed a decrease in the number of oxidized LDL-positive macrophage-derived foam cells in atherosclerotic lesions in the aorta of rabbits fed proanthocyanidin-rich extract. When proanthocyanidin-rich extract was administered orally to rats, proanthocyanidin was detected in the plasma by Porters method but not in the lipoproteins (LDL plus VLDL). In an in vitro experiment using human plasma, proanthocyanidin-rich extract added to the plasma inhibited the oxidation of cholesteryl linoleate in LDL, but not in the LDL isolated after the plasma and the extract were incubated in advance. These results suggested that proanthocyanidins, the major polyphenols in red wine, might trap reactive oxygen species in aqueous series such as plasma and interstitial fluid of the arterial wall, thereby inhibiting oxidation of LDL and showing an antiatherosclerotic activity.

Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces.

PubMed

Ajay, M; Chai, H J; Mustafa, A M; Gilani, A H; Mustafa, M R

2007-02-12

Previous studies have demonstrated the anti-hypertensive effects of Hibiscus sabdariffa L. (HS) in both humans and experimental animals. To explore the mechanisms of the anti-hypertensive effect of the HS, we examined the effects of a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration-dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre-contracted aortic rings, with a greater potency against the alpha(1)-adrenergic receptor agonist. The relaxant effect of HSE was partly dependent on the presence of a functional endothelium as the action was significantly reduced in endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM), significantly blocked the relaxant effects of HSE. Endothelium-dependent and -independent relaxations induced by acetylcholine and sodium nitroprusside, respectively, were significantly enhanced in aortic rings pretreated with HSE when compared to those observed in control aortic rings. The present results demonstrated that HSE has a vasodilator effect in the isolated aortic rings of hypertensive rats. These effects are probably mediated through the endothelium-derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))-influx into vascular smooth muscle cells. The present data further supports previous in vivo findings and the traditional use of HS as an anti-hypertensive agent.

Rabbit aortic endothelial dysfunction by low-density lipoprotein is attenuated by L-arginine, L-ascorbate and pyridoxine

PubMed Central

Ji, Yong; Han, Yi; Diao, Jianxin; Huang, Yan; Chen, Qi; Ferro, Albert

2003-01-01

We investigated the relative effectiveness of L-arginine, L-ascorbate and pyridoxine in preventing the impairment of endothelium-mediated vasorelaxation induced by native low-density lipoprotein (nLDL) from healthy subjects, oxidised LDL (oxLDL, formed by oxidation of nLDL) or nLDL from type II diabetic patients (dLDL). Rabbit aortic rings were exposed to nLDL, dLDL or oxLDL (50–200 mg protein l−1), or corresponding vehicle, following which they were constricted with noradrenaline 10−6 M; concentration–relaxation curves were determined to acetylcholine (ACh), A23187, or sodium nitroprusside (NP), in the absence or presence of L-arginine (10−5–10−3 M), L-ascorbate (10−5–10−3 M) and pyridoxine (0.5–2.0 mM). nLDL, dLDL and oxLDL all inhibited relaxant responses to ACh and A23187, but not to NP, in a concentration-dependent manner (oxLDL>dLDL>nLDL). In the presence of all LDL preparations, L-arginine, L-ascorbate or pyridoxine each improved ACh and A23187 responses, although none completely normalised endothelium-dependent relaxations. The maximal effect of L-arginine occurred at 10−4 M. The combination of L-arginine 10−4 M, L-ascorbate 10−5 M and pyridoxine 2.0 mM was equally effective as L-arginine 10−4 M alone. Our results confirm that nLDL, dLDL and oxLDL exert inhibitory effects on endothelium dependent, but not endothelium independent, relaxation of rabbit aorta. ACh and A23187 responses in the presence of any LDL species can be ameliorated by supplementation with L-arginine, L-ascorbate or pyridoxine, either singly or in combination, with no agent or combination proving superior to L-arginine alone. Nevertheless, ACh and A23187 responses are not completely normalised with such supplements, suggesting that there also exists a component of LDL-induced inhibition of endothelium-mediated vasorelaxation that is independent of the nitric oxide system. PMID:14597596

Vascular ring presenting as dysphagia in an adult woman: a case report.

PubMed

Powell, B L

2017-01-01

A 48-year-old woman was seen in a surgical outpatient clinic with a 2 year history of progressive dysphagia with occasional regurgitation, partially controlled with a proton pump inhibitor. Primary investigations of pH testing and gastroscopy were normal, although a barium swallow study revealed significant hold-up at the aortic arch impression and a posterior right-sided oesophageal impression suggestive of a right-sided aortic arch. A follow-up computed tomography angiogram discovered a vascular ring encircling the trachea and oesophagus, formed by a right-sided aortic arch with aberrant aortic branches, and a Kommerell's diverticulum. It was deemed that the patient's symptoms were related to this vascular ring. The patient underwent stage-one surgery - an extra-anatomic bypass of the double aortic arch and right subclavian artery - and 4 months later a stent graft insertion over the origin of the diverticulum with the aim of complete symptomatic relief. This case presents a common symptom familiar to any clinician (dysphagia), which has been caused by a rare pathology. It is even more unusual that this should present itself in adulthood.

New graft sizing rings for aortic valve reimplantation procedures.

PubMed

Jelenc, Matija; Jelenc, Blaž; Kneževic, Ivan; Klokocovnik, Tomislav

2018-01-01

The objective was to design sizing rings that would enable proper sizing of the graft in reimplantation procedures and to perform leaflet repair before graft implantation. The rings were designed in Autodesk Fusion 360 (San Rafael, CA, USA) and 3D printed using a commercial online 3D printing service. We designed incomplete rings with a low profile and complete rings with a high profile. The complete rings are best suited for reimplantation procedures, whereas low profile C rings are intended for isolated aortic valve repair, where the ascending aorta is not transected. The rings come in sizes corresponding to Vascutek Gelweave graft sizes (Vascutek Terumo, Renfrewshire, Scotland). The ring internal diameters are 5% larger than the designated ring sizes and account for the 5% stretch of the grafts when pressurized. Blades of the rings are placed at 20° intervals. The slits between the blades are designed in such a way that the commissural U-sutures, when put in place and under tension, will lock the ring in position. The rings were successfully used in 10 of our latest reimplantation procedures. After dissection of the aortic root, the commissures were suspended with U-stitches and then the ring was seated onto them. Complete leaflet repair with plication to achieve adequate effective height was then performed, followed by graft implantation. No additional leaflet repair was needed. The newly designed sizing rings enable proper sizing of the graft in reimplantation procedures and enable complete leaflet repair before graft implantation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat.

PubMed

Olatunji-Bello, I I; Odusanya, A J; Raji, I; Ladipo, C O

2007-04-01

Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel.

Deletion of AMPKα1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release.

PubMed

Almabrouk, Tarek A M; Ugusman, Azizah B; Katwan, Omar J; Salt, Ian P; Kennedy, Simon

2017-10-01

Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Endothelium-denuded aortic rings from wild-type (WT; Sv129) and α 1 AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKα1 KO on the secretory profile of PVAT was assessed by elisa. Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. AMPKα1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. © 2016 The British Pharmacological Society.

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

PubMed

Honda, H; Iwata, T; Mochizuki, T; Kogo, H

2000-06-01

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Multidetector Computed Tomography for Congenital Anomalies of the Aortic Arch: Vascular Rings.

PubMed

García-Guereta, Luis; García-Cerro, Estefanía; Bret-Zurita, Montserrat

2016-07-01

The development of multidetector computed tomography has triggered a revolution in the study of the aorta and other large vessels and has replaced angiography in the diagnosis of congenital anomalies of the aortic arch, particularly vascular rings. The major advantage of multidetector computed tomography is that it permits clear 3-dimensional assessment of not only vascular structures, but also airway and esophageal compression. The current update aims to summarize the embryonic development of the aortic arch and the developmental anomalies leading to vascular ring formation and to discuss the current diagnostic and therapeutic role of multidetector computed tomography in this field. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

PubMed

Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

2007-12-01

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits

PubMed Central

Busseuil, D; Shi, Y; Mecteau, M; Brand, G; Kernaleguen, A-E; Thorin, E; Latour, J-G; Rhéaume, E; Tardif, J-C

2008-01-01

Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS. Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness. Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease. PMID:18414386

Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium

PubMed Central

Spradley, Frank T.; Ho, Dao H.

2015-01-01

Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (−PVAT), and endothelium intact (+ENDO) or removed (−ENDO) from Dahl SS rats and control SS.13BN rats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat −PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13BN rats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), produced a similar effect as that seen with −ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13BN rats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in −PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13BN rats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in Dahl SS rats on normal-salt diet. PMID:26608658

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

PubMed

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

[Comparative study on the reflex responses of carotid and aortic baroreceptors in the rabbit].

PubMed

Li, Z; Ho, S Y

1989-08-01

In 81 anesthetized rabbits, the baroreflex control of heart rate (HR), hind-limb vascular resistance (HVR) and renal sympathetic nerve activity (RSNA) was observed during arterial baroreceptor loading and unloading by intravenously injecting phenylephrine (PE) and nitroprusside (NP). The results were as follows: (1) An increase of arterial pressure with PE caused reduction in HR, HVR and RSNA, while a decrease of arterial pressure with NP evoked opposite responses. These reflex responses were reproducible. (2) By either carotid baroreceptor denervation (CBRX) or aortic baroreceptor denervation (ABRX), the reflex changes of HR induced by injecting PE and NP were impaired (P less than 0.01), while the reflex responses in HVP remained unchanged. Despite of the enhanced basal RSNA following ABRX or CBRX, the magnitude of reflex inhibition in RSNA during injecting NP was similar to that before denervation, whereas that of the reflex excitation in RSNA during injecting NP was reduced (P less than 0.05). (3) After complete sino-aortic denervation (SAD), the change of arterial pressure following PE or NP injection was enhanced, but the reflex changes in HR, HVR and RSNA were significantly diminished (P less than 0.001). (4) Vagotomy abolished the residual reflex changes observed after SAD. The results indicate that the aortic and carotid baroreceptors may regulate HR in a simple additive manner, while the aortic baroreceptor seems to be more important. Furthermore, both the aortic and carotid baroreceptors may play important roles for the reflex control of HVR and RSNA, and operate mutually by the way of inhibitory summation.

Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

PubMed Central

Dong, Mei; Zhong, Lin; Chen, Wen Qiang; Ji, Xiao Ping; Zhang, Mei; Zhao, Yu Xia; Li, Li; Yao, Gui Hua; Zhang, Peng Fei; Zhang, Cheng; Zhang, Lei; Zhang, Yun

2012-01-01

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels. PMID:22737253

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit

PubMed Central

LAMB, DAVID J; AVADES, TONY Y; FERNS, GORDON AA

2001-01-01

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25–1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 ± 0.78 vs. 1.33 ± 0.46 µg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 ± 21 IU/mg tissue) compared to the other groups (187 ± 21; 239 ± 53; 201 ± 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 ± 5.5%) and a deficient diet (0 mg/day) (63.1 ± 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 ± 6.3 and 42.8 ± 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population. PMID:11703538

Right cervical aortic arch with aberrant left subclavian artery.

PubMed

Tjang, Yanto S; Aramendi, José I; Crespo, Alejandro; Hamzeh, Gadah; Voces, Roberto; Rodríguez, Miguel A

2008-08-01

The combination of right cervical aortic arch, aberrant retroesophageal left subclavian artery originating from a Kommerell's diverticulum, and a ligamentum arteriosum, constitutes a rare form of vascular ring. Two patients aged 21 days and 54 years, who were diagnosed by multislice 3-dimensional computed tomography and magnetic resonance imaging, underwent surgical division of a vascular ring. The adult required resection of a Kommerell's aneurysm and subclavian artery reimplantation.

Nucleotide-mediated relaxation in guinea-pig aorta: selective inhibition by MRS2179

PubMed Central

Kaiser, Robert A; Buxton, Iain L O

2002-01-01

The vasodilatory effects of nucleotides in the guinea-pig thoracic aorta were examined to determine the relationship between molecular expression and function of P2Y receptors. In aortic rings precontracted with norepinephrine, vasodilatory responses to purine nucleotides exhibited a rank-order of potency of 2-methylthio-ATP>ADP>ATP. Responses to UTP, but not UDP suggested a functional role for P2Y4 but not P2Y6 receptors. Aortic endothelial cells express at least four P2Y receptors; P2Y1, P2Y2, P2Y4 and P2Y6. In primary culture, these cells exhibit desensitizing transient calcium responses characteristic of P2Y1, P2Y2 and P2Y4, but not P2Y6 receptors. UDP had no effect on endothelial cell calcium. The pyrimidinergic receptor agonist UTP is capable of eliciting robust vasodilation in aortic rings and causing calcium responses in cultured guineapig aortic endothelial cells. These responses are equivalent to the maximum responses observed to ATP and ADP. Measurement of intracellular calcium release in response to ATP and 2-methylthio-ATP were similar, however only the 2-methylthio-ATP response was sensitive to the P2Y1 antagonist N6-methyl-2′-deoxyadenosine-3′,5′-bisphosphate (MRS2179). In aortic rings, vasodilatory responses to 2-methylthio-ATP, ATP and ADP were all blocked by pre-incubation of tissues with MRS2179. MRS2179 pretreatment had no effect of the ability of UTP to cause relaxation of norepinephrine responses in aortic rings or the ability of UTP to cause calcium release in aortic endothelial cells. We demonstrate robust effects of purine and pyrimidine nucleotides in guineapig aorta and provide functional and biochemical evidence that MRS2179 is a selective P2Y1 antagonist. PMID:11815389

Development and in vitro/in vivo Evaluation of a Silastic Intravaginal Ring for Mifepristone Delivery.

PubMed

Duan, X; Ning, M

2015-01-01

Preparation and in vitro/in vivo evaluation of mifepristone intravaginal ring formulations were investigated. In the present study, it is reported that a mifepristone intravaginal ring of reservoir design comprising of a mifepristone silicone elastomer core enclosed in a silicone layer. During the preparation of intravaginal ring solid dispersion method was employed which improved the release rate of drug from the intravaginal ring. In vitro release studies performed under sink conditions and the released drug amounts were estimated using UV spectrometry at 310 nm. In addition, the in vivo release profile of in-house devices was evaluated in female New Zealand white rabbits. The rabbit plasma samples were processed and analyzed using a validated HPLC-MS method. Norgestrel was used as internal standard, and plasma samples contained mifepristone and internal standard were deproteinized, and then subjected to HPLC-MS analysis under condition of electrospray ionization in the selected ion monitoring mode. The drug release from intravaginal ring made in house was constant for 21 days in rabbits, which suggested the mifepristone intravaginal ring release system would be useful in clinical practice in the future. The result indicated the in vitro/in vivo correlation is perfect, which explained in vitro release analysis method developed was feasible.

Effect of the positioning of a balloon valve in the aorta on coronary flow during aortic regurgitation.

PubMed

Antonatos, P G; Anthopoulos, L P; Kandyla, D D; Karras, A D; Moulopoulos, S D

1984-07-01

The coronary artery flow changes relative to the function of a catheter-mounted balloon valve used for relief of aortic regurgitation were studied in 10 mongrel dogs. Acute aortic regurgitation was produced by severing the aortic cusps with a long needle. Coronary flow was recorded from the left anterior descending coronary artery through an electromagnetic flowmeter. When the balloon was functioning within the cavity of the left ventricle there were no significant changes in the coronary flow and aortic pressure, except for a slight decrease in the aortic end-diastolic pressure. When it was functioning in the aortic ring the coronary flow increased 6.52 +/- 1.65 ml/min/100 gm of myocardium (p less than 0.001) and became predominantly diastolic. When it was functioning in the ascending aorta the coronary flow decreased 6.22 +/- 1.16 ml/min/100 gm of myocardium (p less than 0.001) and remained predominantly systolic. Finally, when the balloon was functioning in the thoracic aorta the coronary flow did not change significantly. With the balloon functioning in the aortic ring, ascending aorta, or thoracic aorta, there was a significant increase in the aortic end-diastolic pressure and decrease in the pulse pressure distal to the location of the balloon. It is concluded that the location of the balloon valve inserted for relief of aortic regurgitation influences the effect on coronary arterial flow.

Rapid resetting of rabbit aortic baroreceptors and reflex heart rate responses by directional changes in blood pressure.

PubMed

Burke, S L; Dorward, P K; Korner, P I

1986-09-01

In both anaesthetized and conscious rabbits, perivascular balloon inflations slowly raised or lowered mean arterial pressure (M.A.P.), at 1-2 mmHg/s, from resting to various plateau pressures. Deflations then returned the M.A.P. to resting. 'Steady-state' curves relating M.A.P. to unitary aortic baroreceptor firing, integrated aortic nerve activity and heart rate were derived during the primary and return pressure changes and they formed typical hysteresis loops. In single units, return M.A.P.-frequency curves were shifted in the same direction as the primary pressure changes by an average 0.37 mmHg per mmHg change in M.A.P. Shifts were linearly related to the changes in M.A.P. between resting and plateau levels for all pressure rises and for falls less than 30 mmHg. They were established within 30 s and were quantitatively similar to the rapid resetting of baroreceptor function curves found 15 min-2 h after a change in resting M.A.P. (Dorward, Andresen, Burke, Oliver & Korner, 1982). Unit threshold pressures were shifted within 20 s to the same extent as the over-all curve shift to which they contributed. In the whole aortic nerve, return M.A.P.-integrated activity curves were shifted to same degree as unit function curves in both anaesthetized and conscious rabbits. Simultaneous shifts of return reflex M.A.P.-heart rate curves were also seen in conscious rabbits within 30 s. During M.A.P. falls, receptor and reflex hysteresis was similar, but during M.A.P. rises, reflex shifts were double baroreceptor shifts, suggesting the involvement of other pressure-sensitive receptors. We conclude that hysteresis shifts in baroreceptor function curves, which follow the reversal of slow ramp changes in blood pressure are a form of rapid resetting. They are accompanied by rapid resetting of reflex heart rate responses. We regard this as an important mechanism in blood pressure control which produces relatively high-gain reflex responses, during slow directional pressure changes, over a wider range of absolute pressure levels than would otherwise be possible.

Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.

PubMed

Zook, B C; Spiro, I; Hertz, R

1987-08-01

A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls, uterine lymphatics, and in 4 of 13 (31%) rabbits that survived 2 years of treatment, the tumors metastasized to the lungs. Several deciduosarcomas appeared to arise within the spleen or other abdominal organs. Other drug-related lesions included uterine or vaginal polyps, endometrial atrophy, and focal necrosis and mineralization of the uterine wall. Cells from several deciduosarcomas failed to produce tumors in nude mice or to colonize on soft agar. No decidualization or decidual neoplasms were seen in the controls.

Targeting the Nociceptin/Orphanin FQ Receptor for Scleroderma Therapy

DTIC Science & Technology

2016-08-01

quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small- vessel...ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small-vessel myograph. Vasodilation will be determined by

Vascular tissue engineering by computer-aided laser micromachining.

PubMed

Doraiswamy, Anand; Narayan, Roger J

2010-04-28

Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

[Right-side aortic arch with aberrant left subclavian artery and Kommerell's diverticulum. A cause of vascular ring].

PubMed

Tamayo-Espinosa, Tania; Erdmenger-Orellana, Julio; Becerra-Becerra, Rosario; Balderrabano-Saucedo, Norma; Segura-Standford, Begoña

The right-side aortic arch may be associated with aberrant left subclavian artery, in some cases this artery originates from an aneurismal dilation of the aorta called Kommerell's diverticulum. A report is presented on 2 cases of vascular ring formed by a right-side aortic arch, anomalous left subclavian artery, Kommerell's diverticulum and left patent ductus arteriosus. A review the literature was also performed as regards the embryological development and the imaging methods used to help in the diagnosis of this rare vascular anomaly. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

PubMed Central

Siman, Fabiana D. M.; Silveira, Edna A.; Meira, Eduardo F.; da Costa, Carlos P.; Vassallo, Dalton V.; Padilha, Alessandra S.

2012-01-01

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model. PMID:22529948

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

PubMed Central

Lozano-Cuenca, J.; López-Canales, O.A.; Aguilar-Carrasco, J.C.; Villagrana-Zesati, J.R.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; López-Canales, J.S.

2016-01-01

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels. PMID:27464023

Diagnosis of renal disease in rabbits.

PubMed

Harcourt-Brown, Frances Margaret

2013-01-01

There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

PubMed

Zhang, Jifeng; Niimi, Manabu; Yang, Dongshan; Liang, Jingyan; Xu, Jie; Kimura, Tokuhide; Mathew, Anna V; Guo, Yanhong; Fan, Yanbo; Zhu, Tianqing; Song, Jun; Ackermann, Rose; Koike, Yui; Schwendeman, Anna; Lai, Liangxue; Pennathur, Subramaniam; Garcia-Barrio, Minerva; Fan, Jianglin; Chen, Y Eugene

2017-06-01

CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B-containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α-induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet-induced atherosclerosis in rabbits. © 2017 American Heart Association, Inc.

Endothelium-dependent and independent vasorelaxant effects of aqueous extract of Tridax procumbens Lin. leaf in rat aortic rings.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Murtala, Babatunde A

2012-12-01

Tridax procumbens leaf extract induced aortic relaxation in a concentration-dependent manner, for both phenylephrine (PE) and KCl- induced contractions in isolated rat aortic rings. The relaxation effect of the extract on PE-induced contraction was 57% greater than that on KCl- induced contraction. The extract caused dose-dependent relaxations in precontracted isolated rat aorta with phenylephrine; the relaxation was attenuated by the removal of endothelium. However, the relaxation responses to sodium nitroprusside were not significantly abolished by the removal of endothelium. The vasorelaxatory effect of the extract was completely abolished in presence of L-NAME. The results indicate that the vasorelaxant effect of T. procumbens extract is probably mediated by both endothelium-dependent and-independent mechanisms.

Effects of phenylpropanoid and iridoid glycosides on free radical-induced impairment of endothelium-dependent relaxation in rat aortic rings.

PubMed

Ismailoglu, U B; Saracoglu, I; Harput, U S; Sahin-Erdemli, I

2002-02-01

The protective effect of phenylpropanoid glycosides, forsythoside B and alyssonoside, and the iridoid glycoside lamiide, isolated from the aerial parts of Phlomis pungens var. pungens, against free radical-induced impairment of endothelium-dependent relaxation in isolated rat aorta was investigated. Aortic rings were exposed to free radicals by the electrolysis of the physiological bathing solution. Free radical-induced inhibition of the endothelium-dependent relaxation in response to acetylcholine was countered by incubation of the aortic rings before electrolysis with the aqueous extract (200 microg/ml), phenylpropanoid fraction (100 microg/ml) and iridoid fraction (150 microg/ml) of P. pungens var. pungens. Major components of the phenylpropanoid fraction forsythoside B and alyssonoside also prevented the inhibition of the acetylcholine response, at 10(-4) M concentration. However, the major component of iridoid fraction lamiide was found ineffective at the same concentration. The protective activity of phenylpropanoid glycosides against the free radical-induced impairment of endothelium-dependent relaxation may be related to their free radical scavenging property.

A case of complete double aortic arch visualized by transthoracic echocardiography.

PubMed

Saito, Naka; Kato, Shingo; Saito, Noritaka; Nakachi, Tatsuya; Fukui, Kazuki; Iwasawa, Tae; Kosuge, Masami; Kimura, Kazuo

2017-08-01

A case of double aortic arch that was well visualized using transthoracic echocardiography is reported. A 38-year-old man underwent transthoracic echocardiography for the evaluation of dyspnea. A suprasternal view of transthoracic echocardiography showed the ascending aorta bifurcate to left and right aortic arches, with blood flow from the ascending aorta to bilateral aortic arches. The diagnosis of right side-dominant double aortic arch was made, and the patient's symptom was conceivably related to compression of the trachea due to a vascular ring. This report indicates the potential usefulness of transthoracic echocardiography for noninvasive detection of double aortic arch in adults. © 2017, Wiley Periodicals, Inc.

Pentosanpolysulfate coating of silicone reduces encrustation.

PubMed

Zupkas, P; Parsons, C L; Percival, C; Monga, M

2000-08-01

A significant problem associated with catheterization in the urinary tract is the encrustation of the catheter materials. One approach to reducing encrustation is to alter the surface properties of the catheters. We evaluated the effectiveness of coating with pentosanpolysulfate (PPS), a semisynthetic polysaccharide similar to heparin, in reducing encrustation and the foreign-body inflammatory response to silicone stents in the bladders of male New Zealand White rabbits. Sixteen rabbits were divided into three groups to receive placement in their bladders of uncoated (N = 7), PPS-coated (N = 7), or sham matrix-processed silicone rings (N = 2) via open cystotomy. After 50 days of maintenance on normal food and water, all rabbits were sacrificed, and the air-dried, unfixed silicone ring surfaces were examined by scanning electron microscopy. Bladders and remaining silicone rings were removed and preserved separately. Silicone rings, cleaned of all encrustation, were stained with toluidene blue to determine the presence or absence of PPS coating on the surface. Histologic examination revealed normal tissue in bladder sections exposed to coated silicone rings and an inflammatory response in sections from bladders having uncoated silicone rings. Coating with PPS was associated with an eightfold reduction in the amount of encrustation of silicone and a marked reduction in the inflammatory response of the bladder wall to the foreign body. A PPS coating may be useful in reducing the encrustation of long-term indwelling silicone stents or catheters in the human urinary tract.

Reimplantation versus remodelling with ring annuloplasty: comparison of mid-term outcomes after valve-sparing aortic root replacement.

PubMed

Lenoir, Marien; Maesen, Bart; Stevens, Louis-Mathieu; Cartier, Raymond; Demers, Philippe; Poirier, Nancy; Tousch, Michaël; El-Hamamsy, Ismail

2018-02-08

Remodelling with extra-aortic ring annuloplasty has emerged as an alternative approach to root reimplantation. However, no studies have yet compared outcomes between procedures. The aim of this study was to compare mid-term outcomes in patients undergoing reimplantation versus remodelling with extra-aortic annuloplasty. From 2001 to 2017, 142 patients underwent root remodelling with extra-aortic annuloplasty (n = 83, 48 ± 13 years) or a reimplantation technique (n = 59, 48 ± 12 years) at the Montreal Heart Institute. No differences were observed in the incidence of connective tissue disease (24% vs 29%, P = 0.9) or preoperative aortic insufficiency ≥3 (37% vs 23%, P = 0.24). However, in the remodelling group, there were more bicuspid aortic valves (31% vs 9%; P < 0.01), and the mean preoperative aortic annulus diameter was larger (27.2 ± 3.6 mm vs 25.6 ± 2.4 mm; P = 0.01). The mean follow-up duration was 3.9 years (100% complete). There were no hospital deaths and 5 late deaths. At 5 years, overall survival was similar in both groups (100%, P = 0.98). Similarly, 5-year freedom from aortic valve reoperation was equivalent (97 ± 2% in both groups, P = 0.95). Furthermore, 5-year survival free from aortic insufficiency ≥2 or reoperation was 84 ± 5% in the remodelling with annuloplasty group vs 83 ± 6% in the reimplantation group (P = 0.62). The mean annular diameter was 24.3 ± 0.5 mm at 5 years vs 23.6 ± 0.3 mm at discharge in the remodelling group (P = 0.28) and 24.4 ± 0.6 mm vs 23.2 ± 0.3 mm, respectively, in the reimplantation group (P = 0.1). Despite a higher prevalence of bicuspid aortic valves and larger aortic annular diameters, mid-term outcomes after remodelling with extra-aortic annuloplasty and reimplantation are comparable. Extra-aortic ring annuloplasty is effective at stabilizing annular dimensions. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

PubMed

Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

2015-02-25

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1.

PubMed

Lawson, D L; Haught, W H; Mehta, P; Mehta, J L

1996-09-01

Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG-mediated relaxation.

Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points.

PubMed

Chooi, K Yean; Comerford, Andrew; Cremers, Stephanie J; Weinberg, Peter D

2016-07-01

Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. Evans' Blue dye-labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p < 0.05), and the same pattern was seen when only the largest hotspots were considered. The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions. Copyright © 2016. Published by Elsevier Ireland Ltd.

Hypotensive, vasorelaxant and cardiodepressant activities of the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr.

PubMed

Kitic, D; Brankovic, S; Radenkovic, M; Savikin, K; Zdunic, G; Kocic, B; Velickovic-Radovanovic, R

2012-10-01

Sideritis raeseri spp. raeseri Boiss & Heldr is a native plant from the Mediterranean region that is used due to its medicinal and culinary properties. The aim of this study was to evaluate the effects of ethanol extract of S. raeseri on the blood pressure, vascular and cardiac contractions. Arterial blood pressure was registered directly from the carotid artery in the anaesthetized rabbits. Aortic rings and the spontaneously beating atria were mounted in tissue bath. An intravenous injection of extract of S. raeseri (0.025-7.5 mg/kg) caused a dose dependent decrease of the arterial pressure and heart rate, with EC(50) value of 24.31±3.87 mg/kg and 88.14±7.51 mg/kg, respectively. In aortic preparations precontracted with KCl (80 mM), the extract of S. raeseri (0.005-1.5 mg/ml) elicited a vasodilatator action (EC(50) 0.11±0.008 mg/ml). In spontaneously beating rat atria, the extract of S. raeseri (0.005-1.5 mg/ml) produced decrease of chronotropic and inotropic activity (with EC(50) value of 0.63±0.03 mg/ml and 0.40±0.08 mg/ml). Administration of verapamil induced inhibition of force and rate of the atrial contraction. These results demonstrate that the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr can produce hypotension, vasodilatation, negative chronotropic and inotropic effects.

[Changes in endothelium-dependent dilation and α1-adrenoreactivity of rat aorta caused by inducible NO-synthase inhibition after motor activity restrictions].

PubMed

Solodkov, A P; Iatskovskaia, N M

2013-07-01

The aim of work was to study the influence of the highly selective blocker of the inducible NO-synthase (iNOS) of S-methylthiourea on the alteration of the endothelium-dependent vasodilation and α1-adrenoreactivity of the isolated rat aortic rings which underwent a short-term restriction of physical activity. The experiments were carried out on rat aortic rings preparations from female-rats bathed in Krebs-Henseleit solution, bubbled with 95% O2 and 5% CO2 and contracting in isometric mode. Endothelium-dependent dilation was caused by cumulative addition of acetylcholine (10-(10)-10(-4) M) after phenylephrine precontraction(10(-6) M). Adrenoreactivity was assessed through the response to increasing concentrations of α1-adrenergic receptor agonist. The 60-minute immobilization stress, characterized by the increase of the relative weight of the adrenal glands by 19.5%, the concentration of glucocorticoids (twice as much), of NO2/NO3 (stable NO degradation products) by 35%, the reduction in the level of thyroxine (by 16%), triiodothyronine (by 10%) and the increase in thyrotropic hormone by 45%, interleukin-1b (twice as much) and the appearance of tumour necrosis factor alpha in the blood serum, was accompanied by the two types of reaction of isolated aortic rings to acetylcholine and phenylephrine. The first one was expressed in the enhancing of acetylcholine-induced dilation of isolated aortic rings and the reduction of its response to α1-adrenergic stimulant phenylephrine. The second one showed a decrease in the response of isolated aortic rings to acetylcholine and enhancing the response to phenylephrine. But both of these reaction types were eliminated by using highly selective inducible NO-synthase inhibitor with S-methylisothiourea. However, it was differently directed with a different type of reaction. Taken together, these results suggest that the iNOS is formed in the cells of rat aorta under short-term stress. In some cases it can be a source of a large number of NO (coupling state of iNOS), and in another contribute reduce its bioavailability (uncoupling state of iNOS).

Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril.

PubMed

Liu, Yu-Hui; You, Yu; Song, Tao; Wu, Shu-Jing; Liu, Li-Ying

2007-08-01

To explore the effects of angiotensin-converting enzyme (ACE) inhibitors on endothelial dysfunction induced by homocysteine thiolactone (HTL). Both endothelium-dependent relaxation and nondependent relaxation of thoracic aortic rings in rats induced by acetylcholine (Ach) or sodium nitroprusside (SNP) and biochemical parameters including malondialdehyde (MDA) and nitric oxide (NO) were measured in rat isolated aorta. Exposure of aortic rings to HTL (3 to 30 mM) for 90 minutes made a significant inhibition of endothelium-dependent relaxation induced by Ach, decreased contents of NO, and increased MDA concentration in aortic tissue. After incubation of aortic rings with captopril (0.003 to 0.03 mM) attenuated the inhibition of endothelium-dependent relaxation (EDR) and significantly resisted the decrease of NO content and elevation of MDA concentration caused by HTL (30 mmol/L) in aortic tissues, a similarly protective effect was observed when the aortic rings were incubated with both N-acetylcysteine (0.05 mM). Treatment with enalaprilat (0.003 to 0.01 mM) made no significant difference with the HTL (30 mM) group regarding EDR, but enalaprilat (0.03 mM) and losartan (0.03 mM) could partly restore the EDR in response to HTL (30 mM). Captopril was more effective than enalaprilat and losartan in attenuation of the inhibition of on acetylcholine-stimulated aortic relaxation by HTL in the same concentration. Moreover, superoxide dismutase (SOD, 200 U/mL), which is a scavenger of superoxide anions, apocynin (0.03 mM), which is an inhibitor of NADPH oxidase, and l-Arginine (3 mmol/L), a precursor of nitric oxide (NO), could reduce HTL (30 mM)-induced inhibition of EDR. After pretreatment with not only the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME, 0.01 mM) but also the free sulfhydryl group blocking agent p-hydroxymercurybenzoate (PHMB, 0.05 mM) could abolish the protection of captopril and N-acetylcysteine, respectively. These results suggest that mechanisms of endothelial dysfunction induced by HTL may include the decrease of NO and the generation of oxygen free radicals and that captopril can restore the inhibition of EDR induced by HTL in isolated rat aorta, which may be related to scavenging oxygen free radicals and may be sulfhydryl-dependent.

Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

PubMed Central

2010-01-01

Background Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the Pistacia vera nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis. Methods and results Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months. Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration. Conclusions During short-term administration concomitantly with atherogenic diet, both P. vera extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that P. vera dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management. PMID:20633299

Vasorelaxant Action of the Chloroform Fraction of Orthosiphon stamineus via NO/cGMP Pathway, Potassium and Calcium Channels.

PubMed

Yam, Mun Fei; Tan, Chu Shan; Ahmad, Mariam; Ruan, Shibao

2016-01-01

Orthosiphon stamineus Benth. (Lamiaceae) is an important plant in traditional folk medicine that is used to treat hypertension and kidney stones. In humans, this plant has been tested as an addition regiment for antihypertensive treatment. Among the treatments for hypertension, O. stamineus had been to have diuretic and vasorelaxant effects in animal models. There is still very little information regarding the vasorelaxant effect of O. stamineus. Therefore, the present study was designed to investigate the vasorelaxant activity and mechanism of action of the fractions of O. stamineus. The vasorelaxant activity and the underlying mechanisms of the chloroform fraction of the 50% methanolic extract of O. stamineus (CF) was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. CF caused relaxation of the aortic ring pre-contracted with phenylephrine in the presence and absence of endothelium, and pre-contracted with potassium chloride in endothelium-intact aortic ring. In the presence of endothelium, both indomethacin (a nonselective cyclooxygenase inhibitor) and [Formula: see text]-[1,2,4]Oxadiazolo[4,3-[Formula: see text

Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mansson Broberg, Agneta; Grinnemo, Karl-Henrik; Genead, Rami

Aims were to explore if darbepoietin-{alpha} in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.8 mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-{alpha} with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-{alpha} treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-{alpha}. Cell proliferation was about 10 times highermore » in the periinfarct area than in the noninfarcted wall. Darbepoietin-{alpha} treatment led to a decrease of cell proliferation (BrdU, (p < 0.02)) and apoptosis (TUNEL, p < 0.005) with about 30% in the periinfarct area. Darbepoietin-{alpha} and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-{alpha} can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.« less

Inhibition of angiogenic attributes by decursin in endothelial cells and ex vivo rat aortic ring angiogenesis model.

PubMed

Bhat, Tariq A; Moon, Jung S; Lee, Sookyeon; Yim, Dongsool; Singh, Rana P

2011-11-01

The present study was undertaken to observe the inhibition of angiogenesis by decursin. It was the first time to show that decursin offered strong anti-angiogenic activities under the biologically relevant growth (with serum) conditions. Decursin significantly inhibited human umbilical vein endothelial cell (HUVEC) proliferation concomitant with G1 phase cell cycle arrest. Decursin also inhibited HUVEC-capillary tube formation and invasion/migration in a dose-dependant manner which was associated with the suppression of matrix metalloproteinase (MMP) -2 and -9 activities. Decursin suppressed angiogenesis in ex vivo rat aortic ring angiogenesis model where it significantly inhibited blood capillary-network sprouting from rat aortic sections. Taken together, these findings suggested anti-angiogenic activity of decursin in biologically relevant condition, and warrants further pre-clinical studies for its potential clinical usefulness.

Cortisol-21-sulfate (FS) is a specific ligand for intracellular transcortin: demonstration of three types of high affinity corticosteroid binders in bovine aortic cytosol by a combined use of FS and RU 28362.

PubMed

Hayashi, T; Kornel, L

1990-01-01

This paper reports the results of a study on the binding of adrenal steroids in bovine aortic tissue. Using the same method as in our previous study of mineralocorticoid and glucocorticoid binding in rabbit arterial cytosol, we could not demonstrate in the bovine aorta the three types of high affinity binders for these steroids, which we found in the rabbit arteries. In the search for specific markers for each of the three types of binders (glucocorticoid and mineralocorticoid receptors and the transcortin-like intracellular binder), we have found that a conjugated steroid, cortisol-21-sulfate, binds preferentially to the transcortin-like binder, but not to the two receptors. Using this steroid, in combination with the pure synthetic glucocorticoid RU 28362, we were able to clearly discriminate between the three types of corticosteroid binders in bovine aorta.

Protection against atherogenesis with the polymer drag-reducing agent Separan AP-30.

PubMed

Faruqui, F I; Otten, M D; Polimeni, P I

1987-03-01

The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computer-assisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis.

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue.

PubMed

Rebolledo, Alejandro; Rebolledo, Oscar R; Marra, Carlos A; García, María E; Roldán Palomo, Ana R; Rimorini, Laura; Gagliardino, Juan J

2010-10-21

To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic ...

EPA Pesticide Factsheets

Oleic acid (OA) and other fatty acids can become abundant in the systemic circulation after air pollution exposure as endogenously released lipolysis byproducts or by entering the body as a component of air pollution. Vascular damage has been observed with OA infusion, but it is not yet established whether increased circulating OA is able to produce the type of adverse cardiovascular effects associated with exposure to air pollution, or the mechanisms involved with such damage. Based on responses observed upon exposure of cultured endothelial cells, we hypothesized that OA and a hydroxylated metabolite (12-OH OA) would increase vascular tissue injury and impair vascular reactivity. Thoracic descending aorta tissue was collected from male Wistar Kyoto rats, aged 13-16 weeks. Prior to reactivity testing, independent LDH assays were performed with aortic rings to establish a subcytotoxic OA dose. To determine changes in vascular reactivity, aortic ring segments (n=3-4) were exposed for 1 hr to 100 µM OA, 12-OH OA, or an equivalent EtOH vehicle, followed by testing using myography and pharmacologic agents. Only 12-OH OA exposure significantly inhibited acetylcholine-induced endothelium-dependent vasorelaxation in aortic ring segments (25-30% reduction relative to EtOH control), based on maximum relaxation and dose-response. No change was seen in smooth muscle sensitivity to an exogenous nitric oxide source, sodium nitroprusside. Maximum aortic contractile force ge

A novel experimental animal model of arterial stenosis based on endovascular radiofrequency energy application.

PubMed

Lazoura, Olga; Zacharoulis, Dimitris; Kanavou, Theodora; Rountas, Christos; Katsimboulas, Michael; Tzovaras, George; Habib, Nagy

2011-01-01

To develop a new rabbit model of arterial stenosis using endovascular radiofrequency (RF) energy. Ten rabbits were used for multiple endovascular RF applications to the aorta and left common carotid artery through the Habib™ VesCoag™ catheter. Angiography and color Doppler ultrasound were used to assess vessel patency immediately following the procedure and six weeks later. One rabbit was sacrificed following the procedure for histopathologic analysis of the vessel wall. Two rabbits died of aortic and carotid rupture, respectively, immediately after the procedure. The remaining seven rabbits were sacrificed after six-week follow-up for histopathological analysis. Optimal RF generator settings to induce significant arterial stenosis (>50%) without complications were standardized at 24-26 watts (W) for 1.5 min for the aorta and 6 W for 1 min for the common carotid artery. The six-week follow-up showed permanent results in all surviving rabbits. Histopathology revealed intima and medial smooth muscle layer necrosis. We have developed a novel rabbit model of arterial stenosis using endovascular RF energy. Our model is fast, safe, inexpensive, and reproducible. It would be useful for experimental investigations and new therapeutic devices.

Fracture mechanics of shear crack propagation and dissection in the healthy bovine descending aortic media.

PubMed

Haslach, Henry W; Siddiqui, Ahmed; Weerasooriya, Amanda; Nguyen, Ryan; Roshgadol, Jacob; Monforte, Noel; McMahon, Eileen

2018-03-01

This experimental study adopts a fracture mechanics strategy to investigate the mechanical cause of aortic dissection. Inflation of excised healthy bovine aortic rings with a cut longitudinal notch that extends into the media from the intima suggests that an intimal tear may propagate a nearly circumferential-longitudinal rupture surface that is similar to the delamination that occurs in aortic dissection. Radial and 45°-from-radial cut notch orientations, as seen in the thickness surface, produce similar circumferential crack propagation morphologies. Partial cut notches, whose longitudinal length is half the width of the ring, measure the influence of longitudinal material on crack propagation. Such specimens also produce circumferential cracks from the notch root that are visible in the thickness circumferential-radial plane, and often propagate a secondary crack from the base of the notch, visible in the intimal circumferential-longitudinal plane. Inflation of rings with pairs of cut notches demonstrates that a second notch modifies the propagation created in a specimen with a single notch. The circumferential crack propagation is likely a consequence of the laminar medial structure. These fracture surfaces are probably due to non-uniform circumferential shear deformation in the heterogeneous media as the aortic wall expands. The qualitative deformation morphology around the root of the cut notch during inflation is evidence for such shear deformation. The shear apparently results from relative slip in the circumferential direction of collagen fibers. The slip may produce shear in the longitudinal-circumferential plane between medial layers or in the radial-circumferential plane within a medial lamina in an idealized model. Circumferential crack propagation in the media is then a shear mechanical process that might be facilitated by disease of the tissue. An intimal tear of an apparently healthy aortic wall near the aortic arch is life-threatening because it may lead to full rupture or to wall dissection in which delamination of the medial layer extends around most of the aortic circumference. The mechanical events underlying dissection are not definitively established. This experimental fracture mechanics study provides evidence that shear rupture is the main mechanical process underlying aortic dissection. The commonly performed tensile strength tests of aortic tissue are not clinically useful to predict or describe aortic dissection. One implication of the study is that shear tests might produce more fruitful simple assessments of the aortic wall strength. A clinical implication is that when presented with an intimal tear, those who guide care might recommend steps to reduce the shear load on the aorta. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cholesteryl ester transfer protein inhibition enhances endothelial repair and improves endothelial function in the rabbit.

PubMed

Wu, Ben J; Shrestha, Sudichhya; Ong, Kwok L; Johns, Douglas; Hou, Liming; Barter, Philip J; Rye, Kerry-Anne

2015-03-01

High-density lipoproteins (HDLs) can potentially protect against atherosclerosis by multiple mechanisms, including enhancement of endothelial repair and improvement of endothelial function. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, enhances endothelial repair and improves endothelial function in New Zealand White rabbits with balloon injury of the abdominal aorta. New Zealand White rabbits received chow or chow supplemented with 0.07% or 0.14% (wt/wt) des-fluoro-anacetrapib for 8 weeks. Endothelial denudation of the abdominal aorta was carried out after 2 weeks. The animals were euthanized 6 weeks postinjury. Treatment with 0.07% and 0.14% des-fluoro-anacetrapib reduced cholesteryl ester transfer protein activity by 81±4.9% and 92±12%, increased plasma apolipoprotein A-I levels by 1.4±0.1-fold and 1.5±0.1-fold, increased plasma HDL-cholesterol levels by 1.8±0.2-fold and 1.9±0.1-fold, reduced intimal hyperplasia by 37±11% and 51±10%, and inhibited vascular cell proliferation by 25±6.1% and 35±6.7%, respectively. Re-endothelialization of the injured aorta increased from 43±6.7% (control) to 69±6.6% and 76±7.7% in the 0.07% and 0.14% des-fluoro-anacetrapib-treated animals, respectively. Aortic ring relaxation and guanosine 3',5'-cyclic monophosphate production in response to acetylcholine were also improved. Incubation of HDLs from the des-fluoro-anacetrapib-treated animals with human coronary artery endothelial cells increased cell proliferation and migration relative to control. These effects were abolished by knockdown of scavenger receptor-B1 and PDZ domain-containing protein 1 and by pharmacological inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt. Increasing HDL levels by inhibiting cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelium in damaged New Zealand White rabbit aortas in an scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner. © 2015 American Heart Association, Inc.

Prosthetic valve sparing aortic root replacement: an improved technique.

PubMed

Leacche, Marzia; Balaguer, Jorge M; Umakanthan, Ramanan; Byrne, John G

2008-10-01

We describe a modified surgical technique to treat patients with a previous history of isolated aortic valve replacement who now require aortic root replacement for an aneurysmal or dissected aorta. This technique consists of replacing the aortic root with a Dacron conduit, leaving intact the previously implanted prosthesis, and re-implanting the coronary arteries in the Dacron graft. Our technique differs from other techniques in that we do not leave behind any aortic tissue remnant and also in that we use a felt strip to obliterate any gap between the old sewing ring and the newly implanted graft. In our opinion, this promotes better hemostasis. We demonstrate that this technique is safe, feasible, and results in acceptable outcomes.

TIMP‑3 suppresses the proliferation and migration of SMCs from the aortic neck of atherosclerotic AAA in rabbits, via decreased MMP‑2 and MMP‑9 activity, and reduced TNF‑α expression.

PubMed

Zhai, Huan; Qi, Xun; Li, Zixuan; Zhang, Wei; Li, Chenguang; Ji, Lu; Xu, Ke; Zhong, Hongshan

2018-06-26

The present study investigated the role of tissue inhibitor of matrix metalloproteinase‑3 (TIMP‑3) in regulating the proliferation, migration, apoptosis and activity of matrix metalloproteinase (MMP)‑2 and ‑9, during the development of an atherosclerotic abdominal artery aneurysm (AAA). Experiments were conducted using rabbit AAA neck (NA) smooth muscle cells (SMCs), to investigate the potential for TIMP‑3 to be used as a novel stent coating in preventing aortic dilation adjacent to the AAA. The atherosclerotic AAA model was induced in New Zealand white rabbits via a 6‑week high‑cholesterol diet, followed by incubation of the targeted aortic region with elastase. SMCs were isolated from the aorta adjacent to the aneurysm 30 days after AAA model induction, and stimulated with 3, 10, 30 or 100 ng/ml TIMP‑3. Cell proliferation was investigated using Cell Counting Kit‑8 reagent, migration was examined using a Boyden chamber assay and apoptotic rate was analyzed using the Annexin V‑fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA were used to measure the activity of MMP‑2 and MMP‑9, and the expression of tumor necrosis factor‑α (TNF‑α), respectively. Analysis of cell proliferation indicated that 10, 30 and 100 ng/ml TIMP‑3 reduced cell viability. Cell migration was decreased by 10, 30 and 100 ng/ml TIMP‑3. MMP‑2 activity was inhibited by 10, 30 and 100 ng/ml TIMP‑3, and MMP‑9 activity was suppressed by 30 and 100 ng/ml TIMP‑3. The protein levels of secreted TNF‑α were reduced by 10, 30 and 100 ng/ml TIMP‑3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP‑3 to attenuate migration and proliferation, and to inhibit the activity of MMP‑2, MMP‑9 and TNF‑α secretion of NA SMCs. In conclusion, TIMP‑3 may be considered a potential therapeutic drug for use in a novel drug‑eluting stent, to attenuate the progressive dilation of the aortic NA.

Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

PubMed

Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

2018-02-01

 Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations ( r  = 0.3, p  = 0.018 and r  = -0.4, p  = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

PubMed Central

2010-01-01

Aim To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Methods Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Results Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. Conclusions FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function. PMID:20964827

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

PubMed

Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

2003-09-01

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

Long-lasting endothelium-dependent relaxation of isolated arteries caused by an extract from the bark of Combretum leprosum

PubMed Central

Alves, Francisco das Chagas; Cavalcanti, Paulo Marques da Silva; Passaglia, Rita de Cassia Aleixo Tostes; Ballejo, Gustavo

2015-01-01

Objective To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals. Methods Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations. Results In all rings tested, Combretumleprosum extract (1.5μg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances. Conclusions Combretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors. PMID:26466063

Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.

PubMed

Wendell, David C; Friehs, Ingeborg; Samyn, Margaret M; Harmann, Leanne M; LaDisa, John F

2017-10-01

Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

PubMed

Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

2015-12-30

The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment. Kefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

Intravascular application of electrocautery in a rabbit model of abdominal aortic endarterectomy

PubMed Central

Wang, Chuan; Xin, Yi; Li, Na; Li, Diankun; Li, Jingxing; Gu, Chengxiong

2017-01-01

Effective therapies for preventing perioperative complications such as thrombosis and inflammation after coronary endarterectomy (CE) are lacking. Electrocoagulation electrotomes have been routinely used in surgery for their cutting, clotting, and hemostatic properties. As strong flattening tools, their electrocautery function may prevent mechanical intimal-adventitial injury to arterial circulation and attenuate stenosis. The present study investigated the effects of intravascular application of electrocautery on ameliorating inflammation and thrombosis in a rabbit model of abdominal aortic endarterectomy. New Zealand rabbits were randomly divided into the sham, control (endarterectomy), and study (endarterectomy + electrocautery) groups with 10 in each group. Abdominal aortas were partially blocked and intima was removed. Electrocautery was performed with an electrocoagulation electrotome through the entire blocked vessel lumen. Vascular ultrasound parameters, molecular biological and histological characteristics of the abdominal aorta including vascular diameter, blood flow velocity, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and apoptosis rate of vascular endothelial cells (ECs) were evaluated postoperatively by vascular Doppler ultrasound, ELISA, real-time RT-PCR, flow cytometry, and immunofluorescence at various time points. Compared with the endarterectomy + electrocautery group, the isolated endarterectomy group had significantly increased levels and gene expression of TNF-α and IL-6 (P<0.05), and rates of apoptosis of vascular ECs (P<0.05), with gradual vascular stenosis and decreased blood flow velocity. In conclusion, intravascular application of electrocautery has favorable short-term effects on the abdominal aorta and can reduce inflammation in a rabbit model of abdominal aorta endarterectomy. Long-term anti-inflammatory and anti-thrombotic effects on arterial remodeling and the clinical value of electrocautery in CE remain to be determined. PMID:28672932

Intravascular application of electrocautery in a rabbit model of abdominal aortic endarterectomy.

PubMed

Wang, Chuan; Xin, Yi; Li, Na; Li, Diankun; Li, Jingxing; Gu, Chengxiong

2017-07-01

Effective therapies for preventing perioperative complications such as thrombosis and inflammation after coronary endarterectomy (CE) are lacking. Electrocoagulation electrotomes have been routinely used in surgery for their cutting, clotting, and hemostatic properties. As strong flattening tools, their electrocautery function may prevent mechanical intimal-adventitial injury to arterial circulation and attenuate stenosis. The present study investigated the effects of intravascular application of electrocautery on ameliorating inflammation and thrombosis in a rabbit model of abdominal aortic endarterectomy. New Zealand rabbits were randomly divided into the sham, control (endarterectomy), and study (endarterectomy + electrocautery) groups with 10 in each group. Abdominal aortas were partially blocked and intima was removed. Electrocautery was performed with an electrocoagulation electrotome through the entire blocked vessel lumen. Vascular ultrasound parameters, molecular biological and histological characteristics of the abdominal aorta including vascular diameter, blood flow velocity, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and apoptosis rate of vascular endothelial cells (ECs) were evaluated postoperatively by vascular Doppler ultrasound, ELISA, real-time RT-PCR, flow cytometry, and immunofluorescence at various time points. Compared with the endarterectomy + electrocautery group, the isolated endarterectomy group had significantly increased levels and gene expression of TNF-α and IL-6 (P<0.05), and rates of apoptosis of vascular ECs (P<0.05), with gradual vascular stenosis and decreased blood flow velocity. In conclusion, intravascular application of electrocautery has favorable short-term effects on the abdominal aorta and can reduce inflammation in a rabbit model of abdominal aorta endarterectomy. Long-term anti-inflammatory and anti-thrombotic effects on arterial remodeling and the clinical value of electrocautery in CE remain to be determined.

Mechanical Characterization and Material Modeling of Diabetic Aortas in a Rabbit Model.

PubMed

Tong, Jianhua; Yang, F; Li, X; Xu, X; Wang, G X

2018-03-01

Diabetes has been recognized as a major risk factor to cause macrovascular diseases and plays a key role in aortic wall remodeling. However, the effects of diabetes on elastic properties of aortas remain largely unknown and quantitative mechanical data are lacking. Thirty adult rabbits (1.6-2.2 kg) were collected and the type 1 diabetic rabbit model was induced by injection of alloxan. A total of 15 control and 15 diabetic rabbit (abdominal) aortas were harvested. Uniaxial and biaxial tensile tests were performed to measure ultimate tensile strength and to characterize biaxial mechanical behaviors of the aortas. A material model was fitted to the biaxial experimental data to obtain constitutive parameters. Histological and mass fraction analyses were performed to investigate the underlying microstructure and dry weight percentages of elastin and collagen in the control and the diabetic aortas. No statistically significant difference was found in ultimate tensile strength between the control and the diabetic aortas. Regarding biaxial mechanical responses, the diabetic aortas exhibited significantly lower extensibility and significantly higher tissue stiffness than the control aortas. Notably, tissue stiffening occurred in both circumferential and axial directions for the diabetic aortas; however, mechanical anisotropy does not change significantly. The material model was able to fit biaxial experimental data very well. Histology showed that a number of isolated foam cells were embedded in the diabetic aortas and hyperplasia of collagen was identified. The dry weight percentages of collagen within the diabetic aortas increased significantly as compared to the control aortas, whereas no significant change was found for that of elastin. Our data suggest that the diabetes impairs elastic properties and alters microstructure of the aortas and consequently, these changes may further contribute to complex aortic wall remodeling.

"Ring pledget": a new concept for secure apex closure during transapical aortic valve implantation.

PubMed

Astarci, Parla; Glineur, David; Kefer, Joelle; Renkin, Jean; Vanoverschelde, Jean-Louis; El Khoury, Gebrine

2010-03-01

Transapical aortic valve implantation requires puncture of the left ventricle apex and insertion of a 32-French delivery sheath. A critical step in the procedure consists of secure closure of the ventricular apex. We describe 2 cases of apical rupture of 42 transapical aortic valve implantations. Furthermore, we describe the use of a newly designed single circular Teflon pledget that can help to avoid this complication. This pledget provides a more secure and uniform shrinkage of the entire apex to close the defect left by the delivery sheath.

Prosthetic Valve Endocarditis Caused by Bartonella henselae: A Case Report of Molecular Diagnostics Informing Nonsurgical Management

PubMed Central

Bartley, Patricia; Angelakis, Emmanouil; Raoult, Didier; Sampath, Rangarajan; Bonomo, Robert A.

2016-01-01

Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result. This, in turn, permitted early initiation of pathogen-directed therapy and subsequent successful medical management of B henselae prosthetic valve endocarditis and aortic graft infection. PMID:27844027

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

PubMed Central

Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

[Protective effects of polysacchride of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan induced diabetic rats].

PubMed

Huang, Zhi-xuan; Mei, Xue-ting; Xu, Dong-hui; Xu, Shi-bo; Lv, Jun-yi

2005-02-01

To study the protective effects of polysaccharide of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic rats. With the doses of polysaccharide of Spirulina platensis (PSP) and Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by i.g. administration to alloxan induced diabetic rats respectively for 6 weeks. Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The contraction and relaxation response to NE and ACh in aortic rings of the alloxan induced diabetic rats has been studied. The results showed the compound of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum and increase HDL-C than in the alloxan induced diabetic rats. The contraction responses to NE in aortic rings of the alloxan induced diabetic rats were significantly elevated in the normal rats, and the responses to ACh were significantly lower. PSP and PST compound could significantly lower the responses to NE and significantly elevate the responses to ACh in aortic rings of the alloxan induced diabetic rats. PSP and PST compound could decrease blood glucose and could protect the vascular of alloxan induced diabetic rats.

[Feasibility and possibility of Inoue stent graft for thoracic aortic aneurysms].

PubMed

Marui, Akira; Kimura, Takeshi; Tazaki, Junichi; Sakata, Ryuzo; Inoue, Kanji

2011-01-01

Open surgical repair is a traditional treatment for patients with thoracic aortic aneurysms. Despite recent advances in surgical techniques and anesthetic management, the surgical repair of thoracic aortic aneurysms is still associated with significant mortality and morbidity. Endovascular aneurysm repair of thoracic aortic aneurysms is emerging as an alternative method for repair in selected patients. Although endovascular stent grafting is less invasive than open surgical repair, involvement of branch vessels and precipitous curvature of the aortic arch limits the application of stent grafting. Inoue stent graft system consists of soft nitinol ring-type stent which enables very flexible stent graft, and it can well comply with the precipitous curvature of the aortic arch. The system also provides a stent graft with a side branch to manage the left subclavian artery. This system does not require the surgical revascularization of the left subclavian artery. In this report, we show the feasibility and possibility of Inoue stent graft system to manage the aortic arch aneurysm.

Hydrogel Ring for Topical Drug Delivery to the Ocular Posterior Segment.

PubMed

Shikamura, Yuko; Yamazaki, Yoshiko; Matsunaga, Toru; Sato, Takao; Ohtori, Akira; Tojo, Kakuji

2016-05-01

To investigate the efficacy of a topical hydrogel ring for drug delivery to the posterior segment of the rabbit eye. Novel hydrogel corneal lenses (CL), scleral/corneal lenses (S/CL), and rings were prepared using poly(hydroxyethyl methacrylate). The devices were immersed in 0.3% ofloxacin ophthalmic solution (OOS) to homogeneously distribute the drug throughout the hydrogel. The medicated CL, S/CL, Ring 1 (standard ring), or Ring 2 (shape-optimized ring) was applied to the surface of the cornea, cornea/bulbar conjunctiva, or bulbar conjunctiva of albino rabbits, respectively. Medicated rings did not touch the corneal surface. In another group, one OOS drop was administered to the eye. After 0.25-8 hours, the hydrogel devices were removed and ocular tissues were harvested. High-performance liquid chromatography (HPLC) was used to measure the ofloxacin concentration in the devices and tissues. The drug concentrations in the posterior segment tissues were compared among ofloxacin delivery methods. One hour after placement, eyes treated with Ring 1 or S/CL had markedly higher ofloxacin levels in the posterior segment tissues (conjunctiva, sclera, and retina/choroid) than eyes treated with topical OOS or a CL. Lower levels of ofloxacin were found in anterior segment tissues (cornea and aqueous humor) in eyes treated with Ring 1 compared to those treated with S/CL. Ring 2 most effectively delivered ofloxacin to the retina/choroid. The tissue ofloxacin concentration in the fellow eye was markedly lower than the eye treated with Ring 2. Our results suggest that hydrogel rings are effective in delivering topical ophthalmic drugs to the posterior segment. The drugs are most likely delivered via the transconjunctival/scleral route by lateral diffusion across the bulbar conjunctiva and through the sclera. Systemic drug delivery to the posterior segment is minimal.

Multidetector-row computed tomography of thoracic aortic anomalies in dogs and cats: Patent ductus arteriosus and vascular rings

PubMed Central

2011-01-01

Background Diagnosis of extracardiac intrathoracic vascular anomalies is of clinical importance, but remains challenging. Traditional imaging modalities, such as radiography, echocardiography, and angiography, are inherently limited by the difficulties of a 2-dimensional approach to a 3-dimensional object. We postulated that accurate characterization of malformations of the aorta would benefit from 3-dimensional assessment. Therefore, multidetector-row computed tomography (MDCT) was chosen as a 3-dimensional, new, and noninvasive imaging technique. The purpose of this study was to evaluate patients with 2 common diseases of the intrathoracic aorta, either patent ductus arteriosus or vascular ring anomaly, by contrast-enhanced 64-row computed tomography. Results Electrocardiography (ECG)-gated and thoracic nongated MDCT images were reviewed in identified cases of either a patent ductus arteriosus or vascular ring anomaly. Ductal size and morphology were determined in 6 dogs that underwent ECG-gated MDCT. Vascular ring anomalies were characterized in 7 dogs and 3 cats by ECG-gated MDCT or by a nongated thoracic standard protocol. Cardiac ECG-gated MDCT clearly displayed the morphology, length, and caliber of the patent ductus arteriosus in 6 affected dogs. Persistent right aortic arch was identified in 10 animals, 8 of which showed a coexisting aberrant left subclavian artery. A mild dilation of the proximal portion of the aberrant subclavian artery near its origin of the aorta was present in 4 dogs, and a diverticulum analogous to the human Kommerell's diverticulum was present in 2 cats. Conclusions Contrast-enhanced MDCT imaging of thoracic anomalies gives valuable information about the exact aortic arch configuration. Furthermore, MDCT was able to characterize the vascular branching patterns in dogs and cats with a persistent right aortic arch and the morphology and size of the patent ductus arteriosus in affected dogs. This additional information can be of help with regard to improved diagnoses of thoracic anomalies and the planning of surgical interventions. PMID:21943366

Vascular response of ruthenium tetraamines in aortic ring from normotensive rats.

PubMed

Conceição-Vertamatti, Ana Gabriela; Ramos, Luiz Alberto Ferreira; Calandreli, Ivy; Chiba, Aline Nunes; Franco, Douglas Wagner; Tfouni, Elia; Grassi-Kassisse, Dora Maria

2015-03-01

Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. To evaluate the vascular response of the tetraamines trans-[Ru(II)(NH3)4(Py)(NO)](3+), trans-[Ru(II)(Cl)(NO) (cyclan)](PF6)2, and trans-[Ru(II)(NH3)4(4-acPy)(NO)](3+). Aortic rings were contracted with noradrenaline (10(-6) M). After voltage stabilization, a single concentration (10(-6) M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10(-6) M and sodium nitroprusside at 10(-6) M as well as by histological examination. Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10(-6) M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model.

PubMed

Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

2015-01-01

To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.

Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

PubMed Central

Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

2015-01-01

Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ran; Xie, Jun; Wu, Han

Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4more » protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular angiogenesis in db/db mice.« less

Vascular activation of K+ channels and Na+-K+ ATPase activity of estrogen-deficient female rats.

PubMed

Ribeiro Junior, Rogério Faustino; Fiorim, Jonaina; Marques, Vinicius Bermond; de Sousa Ronconi, Karoline; Botelho, Tatiani; Grando, Marcella D; Bendhack, Lusiane M; Vassallo, Dalton Valentim; Stefanon, Ivanita

2017-12-01

The goal of the present study was to evaluate vascular potassium channels and Na + -K + -ATPase activity in estrogen deficient female rats. Female rats that underwent ovariectomy were assigned to receive daily treatment with placebo (OVX) or estrogen replacement (OVX+E2, 1mg/kg, once a week, i.m.). Aortic rings were used to examine the involvement of K + channels and Na + -K + -ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100μM) and K + channels blockers: tetraethylammonium (TEA, 5mM), 4-aminopyridine (4-AP, 5mM), iberiotoxin (IbTX, 30nM), apamin (0.5mM), charybdotoxin (ChTX, 0.1mM) and iberiotoxin plus apamin. When aortic rings were pre-contracted with KCl (60mM) or pre-incubated with TEA (5mM), 4-aminopyridine (4-AP, 5mM) and iberiotoxin (IbTX, 30nM) plus apamin (0.5μM), the ACh-induced relaxation was less effective in the ovariectomized group. Additionally, 4-AP and IbTX decreased the relaxation by sodium nitroprusside in all groups but this reduction was greater in the ovariectomized group. Estrogen deficiency also increased aortic functional Na + -K + ATPase activity evaluated by K + -induced relaxation. L-NAME or endothelium removal were not able to block the increase in aortic functional Na + -K + ATPase activity, however, TEA (5mM) restored this increase to the control level. We also found that estrogen deficiency increased superoxide anion production and reduced nitric oxide release in aortic ring from ovariectomized animals. In summary, our results emphasize that the process underlying ACh-induced relaxation is preserved in ovariectomized animals due to the activation of K + channels and increased Na + -K + ATPase activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative analysis of the heme iron electronic structure and stereochemistry in tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a using Mössbauer spectroscopy with a high velocity resolution

NASA Astrophysics Data System (ADS)

Alenkina, I. V.; Kumar, A.; Berkovsky, A. L.; Oshtrakh, M. I.

2018-02-01

A comparative study of tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a in the oxy- and deoxy-forms was carried out using 57Fe Mössbauer spectroscopy with a high velocity resolution in order to analyze the heme iron electronic structure and stereochemistry in relation to the Mössbauer hyperfine parameters. The Mössbauer spectra of tetrameric rabbit hemoglobin in both forms were fitted using two quadrupole doublets related to the 57Fe in ɑ- and β-subunits. In contrast, the Mössbauer spectra of monomeric soybean leghemoglobin a were fitted using: (i) two quadrupole doublets for the oxy-form related to two conformational states of the distal His E7 imidazole ring and different hydrogen bonding of oxygen molecule in the oxy-form and (ii) using three quadrupole doublets for deoxy-form related to three conformational states of the proximal His F8 imidazole ring. Small variations of Mössbauer hyperfine parameters related to small differences in the heme iron electronic structure and stereochemistry in tetrameric rabbit hemoglobin and monomeric soybean leghemoglobin a are discussed.

Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

PubMed

Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

2018-04-09

Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

Double Aortic Arch With Previously Undescribed Head and Neck Vessel Branching.

PubMed

Hashemi, Sassan; Parks, W James; Sallee, Denver; Slesnick, Timothy

2017-04-01

Vascular ring in the form of a double aortic arch is a rare anomaly that can cause airway compression. It occasionally occurs with unusual head and neck vessel branching. A 5-year-old boy with chronic respiratory symptoms was referred because of a tracheal indentation on his chest x-ray. Magnetic resonance imaging showed a double aortic arch with arch origins of a common carotid, vertebral, and subclavian on the right and internal and external carotids, vertebral, and subclavian arteries on the left. Our case represents, to our knowledge, the first report of a double aortic arch with 7 separate vessels arising from the transverse arches. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats

PubMed Central

2014-01-01

Background Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Methods Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Results Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. Conclusions These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function. PMID:24993607

Vasorelaxant effects of aqueous leaf extract of Tridax procumbens on aortic smooth muscle isolated from the rat.

PubMed

Salahdeen, Hussein M; Murtala, Babatunde A

2012-01-01

Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats.

PubMed

de Moraes, Camila; Davel, Ana Paula Couto; Rossoni, Luciana Venturini; Antunes, Edson; Zanesco, Angelina

2008-05-29

Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70-80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. High caloric diet increased triglycerides concentration (SDD: 216 +/- 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 +/- 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 +/- 0.1 and TRD: 1.24 +/- 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 +/- 0.1 and SDD: 2.57 +/- 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 +/- 6; TR: 140 +/- 8; SDD: 156 +/- 8 and TRD 153 +/- 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 +/- 4; TR: 28 +/- 6; SDD: 27 +/- 3 and TRD: 30 +/- 2 microM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Modulation of the pharmacological actions of nitrovasodilators by methylene blue and pyocyanin.

PubMed Central

Gryglewski, R. J.; Zembowicz, A.; Salvemini, D.; Taylor, G. W.; Vane, J. R.

1992-01-01

1. In superfused precontracted strips of rabbit aorta, methylene blue (MeB) or pyocyanin (Pyo, 1-hydroxy-5-methyl phenazinum betaine) at concentrations of 1-10 microM inhibited relaxations induced by endothelium-derived relaxing factor (EDRF), glyceryl trinitrate (GTN), S-nitroso-N-acetyl-penicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1). However, the vasorelaxant actions of sodium nitroprusside (NaNP) or sodium nitrite (NaNO2) were enhanced by MeB or Pyo. Oxyhaemoglobin (HbO2, 1 microM) inhibited the activities of EDRF and all of the nitrovasodilators studied. Vascular preparations were not relaxed by Pyo unless pretreated with NaNP (0.05-10 microM). 2. In bathed, precontracted rings of rabbit aorta, Pyo (10 microM) produced a shift to the left of the cumulative concentration-response curve for NaNP (0.01-10 microM). The rise in guanosine-3':5'-cyclic monophosphate (cyclic GMP) content of aortic tissue was also enhanced. 3. The vasorelaxant potency of NaNP (30 microM) at pH 5-8 and at 37 degrees C remained unchanged over 2.5 h while a solution of SNAP (30 microM) progressively lost its biological activity over 60 min. The in vitro degradation of the biological activity of SNAP was accelerated by MeB (150 microM) or Pyo (150 microM), whereas the vasorelaxant potency NaNP (30 microM) was doubled when incubated with MeB or Pyo. 4. In human platelet-rich plasma, MeB or Pyo (0.3-3.0 microM) uncovered an anti-aggregatory action of subthreshold concentrations of NaNP (4-8 microM). This was abrogated by HbO2 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1327388

Role of inducible nitric oxide synthase in endothelium‐independent relaxation to raloxifene in rat aorta

PubMed Central

Au, Chak Leung; Tsang, Suk Ying; Lau, Chi Wai; Yao, Xiaoqiang; Cai, Zongwei

2017-01-01

Background and Purpose Raloxifene can induce both endothelium‐dependent and ‐independent relaxation in different arteries. However, the underlying mechanisms by which raloxifene triggers endothelium‐independent relaxation are still incompletely understood. The purpose of present study was to examine the roles of NOSs and Ca2+ channels in the relaxant response to raloxifene in the rat isolated, endothelium‐denuded aorta. Experimental Approach Changes in isometric tension, cGMP, nitrite, inducible NOS protein expression and distribution in response to raloxifene in endothelium‐denuded aortic rings were studied by organ baths, radioimmunoassay, Griess reaction, western blot and immunohistochemistry respectively. Key Results Raloxifene reduced the contraction to CaCl2 in a Ca2+‐free, high K+‐containing solution in intact aortic rings. Raloxifene also acutely relaxed the aorta primarily through an endothelium‐independent mechanism involving NO, mostly from inducible NOS (iNOS) in vascular smooth muscle layers. This effect of raloxifene involved the generation of cGMP and nitrite. Also, it was genomic in nature, as it was inhibited by a classical oestrogen receptor antagonist and inhibitors of RNA and protein synthesis. Raloxifene‐induced stimulation of iNOS gene expression was partly mediated through activation of the NF‐κB pathway. Raloxifene was more potent than 17β‐estradiol or tamoxifen at relaxing endothelium‐denuded aortic rings by stimulation of iNOS. Conclusions and Implications Raloxifene‐mediated vasorelaxation in rat aorta is independent of a functional endothelium and is mediated by oestrogen receptors and NF‐κB. This effect is mainly mediated through an enhanced production of NO, cGMP and nitrite, via the induction of iNOS and inhibition of calcium influx through Ca2+ channels in rat aortic smooth muscle. PMID:28138957

Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis.

PubMed Central

Rouse, M S; Steckelberg, J M; Brandt, C M; Patel, R; Miro, J M; Wilson, W R

1997-01-01

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model. PMID:9257739

Atheroprotective effects of Cuphea carthagenensis (Jacq.) J. F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet.

PubMed

Barboza, Lorena Neris; Lívero, Francislaine Aparecida Dos Reis; Prando, Thiago Bruno Lima; Ribeiro, Rita de Cassia Lima; Lourenço, Emerson Luiz Botelho; Budel, Jane Manfron; de Souza, Lauro Mera; Acco, Alexandra; Dalsenter, Paulo Roberto; Gasparotto, Arquimedes

2016-07-01

Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the descending aorta.

Oesophageal foreign body and a double aortic arch: rare dual pathology.

PubMed

O'Connor, T E; Cooney, T

2009-12-01

We report the rare case of an oesophageal foreign body which lodged above the site of oesophageal compression by a double aortic arch. Case report and a review of the literature surrounding the classification, embryology, diagnosis and management of vascular rings and slings. An eight-month-old male infant presented with symptoms of tracheal compression following ingestion of an oesophageal foreign body. Following removal of the oesophageal foreign body, the infant's symptoms improved initially. However, subsequent recurrence of respiratory symptoms lead to a repeat bronchoscopy and the diagnosis of a coexisting double aortic arch, causing tracheal and oesophageal compression. To our knowledge, this is only the second reported case of a double aortic arch being diagnosed in a patient following removal of an oesophageal foreign body.

[Effects of intermediate conductance calcium-activated potassium channel blocker TARAM-34 on β-glycerophosphate induced vascular smooth muscle cells calcification].

PubMed

Zhang, S L; Xu, J S; Yang, S; Bai, Y L; Zhang, J X; Cui, L W; Yu, Q Y

2016-06-24

To observe the role of TRAM-34 (1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole), the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1), on β-glycerophosphate induced vascular calcification in vitro. Vascular smooth muscle cells(VSMCs) were obtained from rat thoracic aorta, and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10% fetal bovine serum), high phosphorus group (cultured in DMEM with 10% fetal bovine serum and 10% β-glycerophosphate) and TRAM-34 group(20 nmol/L TRAM-34 was added into high phosphorus DMEM). Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2(Runx2)was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit. (1) Compared with control group, calcification was significantly increased in high phosphorus group ((121.67±6.17) mg/g vs. (84.38±8.17) mg/g, P<0.05) and this effect could be attenuated by TRAM-34 ((93.31±11.36) mg/g, P<0.05 vs. high phosphorus group) after 12 days culture. Similar results were found in aortic rings cultured for 12 days-high phosphorus group: (7.17±0.57) mg/g vs. (1.18±0.13) mg/g (P<0.05) and TRAM-34: (4.71±0.42) mg/g, P<0.05 vs. high phosphorus group.(2) Compared with control group, the calcium influx was higher in high phosphorus group (349.22±40.47 vs. 151.67±16.94, P<0.05) and reduced in TRAM-34 group (194.67±22.21, P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days. (3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630±0.033 vs.0.340±0.058 and 0.865±0.031 vs.0.414±0.011, both P<0.05) and lower in TRAM-34 group (0.399±0.023 and 0.575±0.014, both P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days.Besides, compared with high phosphorus group, the expression of Runx2 was decreased in control group(0.113±0.010 vs.0.067±0.008, P<0.05) and TRAM-34 group (0.069±0.006, P<0.05) after aortic rings were cultured for 4 days. (4) Compared with control group, the activity of ALP was significantly increased in high phosphorus group (96.56±9.84 vs.46.92±4.60, P<0.05) and decreased in TRAM-34 group(70.20±8.41, P<0.05 vs. high phosphorus group) in VSMCs simulated for 12 days. KCa3.1 blocker TRAM-34 can inhibit β-glycerophosphate induced VSMCs and aortic ring calcification through inhibiting calcium influx, downregulating Runx2 expression and attenuating osteogenic differentiation.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Development of a microfabricated artificial limbus with micropockets for cell delivery to the cornea.

PubMed

Ortega, Ílida; Deshpande, Pallavi; Gill, Andrew A; MacNeil, Sheila; Claeyssens, Frederik

2013-06-01

The aim of this study was to develop a synthetic alternative to the human corneal limbus for use initially as an ex vivo model in which to study corneal stem cell function within a niche environment and ultimately to develop an implantable limbus for future clinical use. Microstereolithography was used for the fabrication of polyethylene glycol diacrylate (PEGDA) based rings on a macroscopic (1.2 cm) scale containing unique microfeatures (pockets) which were then modified with fibronectin to promote cell adhesion. These rings were designed to mimic the limbal area of the eye containing structures of the approximate size and shape of the stem cell microenvironments found in the palisades of Vogt. The attachment of rabbit limbal fibroblasts and rabbit limbal epithelial cells to the PEGDA rings was increased by pretreating the microfabricated structures with biotinylated fibronectin. Cell outgrowth from fibronectin coated microfabricated structures was 50% greater than from rings without structures or fibronectin coating. The cell loaded rings were then placed on an ex vivo wounded cornea model and the outgrowth of cells to form a multilayered epithelium was observed. We suggest this is a new approach to investigating limbal stem cells niches and the first steps towards a new approach for corneal regeneration.

Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

PubMed

Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

2017-06-01

Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (P<.05) ameliorated by the administration of BA juice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model.

PubMed

Wang, Liang; Fumoto, Toshio; Masumoto, Saeko; Shoji, Toshihiko; Miura, Tomisato; Naraoka, Masato; Matsuda, Naoya; Imaizumi, Tadaatsu; Ohkuma, Hiroki

2017-03-01

Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect. After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology. Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group. This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Hemodynamics in an Aorta with Bicuspid and Trileaflet Valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2015-11-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as ascending aortic aneurysm, aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. Two main hypotheses - the genetic and the hemodynamic are discussed in literature to explain the development and progression of aortopathies in patients with BAV. In this study we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the Curvilinear Immersed Boundary (CURVIB) method coupled with an efficient thin-shell finite element (TS-FE) formulation for tissues to carry out fluid-structure interaction simulations of a healthy tri-leaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large scale flow patterns in the ascending aorta; and the shear stress magnitude on the aortic wall. The computed results are in qualitative agreement with in vivo Magnetic Resonance Imaging (MRI) data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation. This work is supported by the Lillehei Heart Institute at the University of Minnesota and the Minnesota Supercomputing Institute.

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels.

PubMed

Gilani, Anwarul Hassan; Mandukhail, Saf-ur-Rehman; Iqbal, Javeid; Yasinzai, Masoom; Aziz, Nauman; Khan, Aslam; Najeeb-ur-Rehman

2010-01-13

Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of Morinda citrifolia roots (Mc.Cr). The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K(+) induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca(++), similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 μM) in normal- Ca(++) and Ca(++)-free kreb solutions and by high K(+), similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 μM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 μM) and removal of endothelium. These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of Morinda citrifolia in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels

PubMed Central

2010-01-01

Background Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Methods Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of Morinda citrifolia roots (Mc.Cr). Results The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K+ induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca++, similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 μM) in normal- Ca++ and Ca++-free Kerb's solutions and by high K+, similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 μM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 μM) and removal of endothelium. Conclusions These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of Morinda citrifolia in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant. PMID:20070879

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

PubMed Central

Sendobry, Sandra M; Cornicelli, Joseph A; Welch, Kathryn; Bocan, Thomas; Tait, Bradley; Trivedi, Bharat K; Colbry, Norman; Dyer, Richard D; Feinmark, Steven J; Daugherty, Alan

1997-01-01

15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a Ki of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the Ki.Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg−1, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated Ki (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg−1 (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.Results of these studies are consistent with a role for 15-LO in atherogenesis. PMID:9105693

Anti-atherosclerotic effects of garlic preparation in freeze injury model of atherosclerosis in cholesterol-fed rabbits.

PubMed

Sobenin, Igor A; Andrianova, Irina V; Lakunin, Konstantin Y; Karagodin, Vasilii P; Bobryshev, Yuri V; Orekhov, Alexander N

2016-10-15

Garlic (Allium sativum L.) is one of the most popular substances used to reduce various risks associated with cardiovascular disease. However, little is known on the direct effects of garlic on atherosclerosis. In the present study we have examined the effect of per oral administration of the time-released garlic herbal preparation on serum atherogenicity and formation of intimal thickening after freeze injury in cholesterol-fed rabbits. Group 1 rabbits maintained on the standard cholesterol-rich diet served as the control. Group 2 rabbits were fed the cholesterol-rich diet and treated with garlic preparation containing 300 mg garlic powder. Local thickening of the aortic media (i.e., the neointima formation) in the freeze injury zone was observed in all the rabbits. Regular garlic preparation therapy prevented the neointima formation and the accumulation of free and esterified cholesterol, triglycerides, phospholipids and collagen in the neointima, the effects being statistically significant. Garlic preparation also decreased serum lipid content by 1.5-fold and lowered atherogenic activity of blood serum (ability to induce lipid accumulation in cultured cells) induced by cholesterol-rich diet. The results obtained indicate that garlic preparation prevents the development of cholesterol-induced experimental atherosclerosis and possesses the direct anti-atherogenic activity. Copyright © 2015 Elsevier GmbH. All rights reserved.

HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.

PubMed

Merlet, Nolwenn; Busseuil, David; Mihalache-Avram, Teodora; Mecteau, Melanie; Shi, Yanfen; Nachar, Walid; Brand, Genevieve; Brodeur, Mathieu R; Charpentier, Daniel; Rhainds, David; Sy, Gavin; Schwendeman, Anna; Lalwani, Narendra; Dasseux, Jean-Louis; Rhéaume, Eric; Tardif, Jean-Claude

2016-07-15

High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anomalous origin of the left innominate (brachiocephalic) artery in the right aortic arch: How can it be anomalous when the left innominate artery is absent?

PubMed

Raimondi, Francesca; Bonnet, Damien; Geva, Tal; Sanders, Stephen P

2016-01-01

An unusual case of a rare vascular ring, which has been called right aortic arch with aberrant left innominate artery, is presented. The appearance of this case led to the realization that there is really no innominate artery present in this anomaly but only the left dorsal aorta. We present a clarification of the nature and likely development of the vessels present.

Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

PubMed Central

Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

2014-01-01

Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+ dep) compared with Na+-independent (Na+ indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na+ indep transport in SHR compared with WKY rats. Total and Na+ dep component of transport were increased, but Na+ indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+ indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na+-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR. PMID:24587332

Comparative hemodynamics in an aorta with bicuspid and trileaflet valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2016-04-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. There are two main hypotheses to explain the increase prevalence of aortopathies in patients with BAV: the genetic and the hemodynamic. In this study, we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the curvilinear immersed boundary method coupled with an efficient thin-shell finite-element formulation for tissues to carry out fluid-structure interaction simulations of a healthy trileaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large-scale flow patterns in the ascending aorta; the shear stress magnitude, directions, and dynamics on the heart valve surfaces. The computed results are in qualitative agreement with in vivo magnetic resonance imaging data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation.

Vasorelaxant effect of formononetin in the rat thoracic aorta and its mechanisms.

PubMed

Zhao, Yan; Chen, Bai-Nian; Wang, Shou-Bao; Wang, Shao-Hua; Du, Guan-Hua

2012-01-01

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N(ω)-nitro-L-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca²⁺-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca²⁺ channels. The opening of K⁺ channels might also be one of the mechanisms of formononetin-induced vasorelaxation.

Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo.

PubMed Central

Mülsch, A.; Bara, A.; Mordvintcev, P.; Vanin, A.; Busse, R.

1995-01-01

1. In the present study we assessed the formation of nitric oxide (NO) from classical and thiol-containing organic nitrates in vascular tissues and organs of anaesthetized rabbits, and established a relationship between the relaxant response elicited by nitroglycerin (NTG) and NO formation in the rabbit isolated aorta. Furthermore, the effect of isolated cytochrome P450 on NO formation from organic nitrates was investigated. 2. Rabbits received diethyldithiocarbamate (DETC; 200 mg kg-1 initial bolus i.p. and 200 mg kg-1 during 20 min, i.v.) and either saline, or one of the following organic nitrates: nitroglycerin (NTG, 0.5 mg kg-1), isosorbide dinitrate (ISDN), N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 3672), S-carboxyethyl-N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 5185), at 10 mg kg-1 each. After 20 min the animals were killed, blood vessels and organs were removed, and subsequently analyzed for spin-trapped NO by cryogenic electron spin resonance (e.s.r.) spectroscopy. 3. In the saline-treated control group, NO remained below the detection limit in all vessels and organs. In contrast, all of the nitrates tested elicited measurable NO formation, which was higher in organs (liver, kidney, heart, lung, spleen) (up to 4.8 nmol g-1 20 min-1) than in blood vessels (vena cava, mesenteric bed, femoral artery, aorta) (up to 0.7 nmol g-1 20 min-1). Classical organic nitrates (NTG, ISDN) formed NO preferentially in the mesenteric bed and the vena cava, while the SPM compounds elicited comparable NO formation in veins and arteries. 4. Using a similar spin trapping technique, NO formation was assessed in vitro in phenylephrine-precontracted rabbit aortic rings. The maximal relaxation elicited by a first exposure (10 min) to NTG (0.3 to 10 microM) was positively correlated (r = 0.8) with the net increase (NTG minus basal) of NO spin-trapped during a second exposure to the same concentration of NTG in the presence of DETC. 5. Cytochrome P450 purified from rabbit liver enhanced NO formation in a NADPH-dependent fashion from NTG, but not from the other nitrates, as assessed by activation of purified soluble guanylyl cyclase. 6. We conclude that the vessel selective action of different organic nitrates in vivo reflects differences in vascular NO formation. Thus, efficient preload reduction by classical organic nitrates can be accounted for by higher NO formation in venous capacitance as compared to arterial conductance and resistance vessels. In contrast, NO is released from cysteine-containing nitrates (SPMs) to a similar extent in arteries and veins, presumably independently of an organic nitrate-specific biotransformation. Limited tissue bioavailability of NTG and ISDN might account for low NO formation in the aorta, while true differences in biotransformation seem to account for differences in NO formation in the other vascular tissues. PMID:8590999

Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling

PubMed Central

Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun; Wang, Xiaoke; Kherada, Nisharahmed; Desikan, Rajagopal; Mihai, Georgeta; Burns, Patrick; Sun, Qinghua; Rajagopalan, Sanjay

2016-01-01

Objective Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. Methods and Results Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. Conclusion Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID:26859892

Mechanisms of the palmitoylcarnitine-induced response in vascular endothelial cells.

PubMed

Taki, H; Muraki, K; Imaizumi, Y; Watanabe, M

1999-09-01

The mechanisms of Ca2+ mobilization induced by palmitoylcarnitine (Palcar) in rabbit aortic endothelial cells (ETCs) were examined using electrophysiological techniques. The results obtained were compared with those induced by acetylcholine (ACh). When a rabbit aortic muscle preparation with an intact endothelium was treated with 10 microM Palcar, the ACh-induced relaxation was markedly attenuated, whereas endothelium-independent relaxation caused by sodium nitroprusside was not affected. Under perforated-patch whole-cell-clamp conditions, the application of Palcar over the concentration range 0.3 and 10 microM elicited a slowly activating outward current (IPalcar-out), whereas ACh induced a rapidly activating outward current (IACh). A potassium channel blocker, 4-aminopyridine, significantly inhibited both IPalcar-out and IACh. Removal of external Ca2+ almost abolished IPalcar-out. Under the same conditions, however, IACh remained transient. Addition of cation channel blockers SK&F96365 and La3+ inhibited IPalcar-out more effectively than IACh. Application of staurosporine, an inhibitor of protein kinase C, affected neither IACh nor IPalcar-out. In contrast, treatment of ETCs with pertussis toxin (PTX) reduced IACh and almost abolished IPalcar-out. These findings demonstrate that, in ETCs, Palcar induces Ca2+ influx via the activation of PTX-sensitive GTP-binding protein, leading to the activation of Ca(2+)-dependent K+ current and hyperpolarization of the cell.

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

PubMed

Alavi, M Z; Richardson, M; Moore, S

1989-02-01

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.

Cloning and pharmacological characterization of the rabbit bradykinin B2 receptor.

PubMed

Bachvarov, D R; Saint-Jacques, E; Larrivée, J F; Levesque, L; Rioux, F; Drapeau, G; Marceau, F

1995-12-01

Degenerate primers, corresponding to consensus sequences of third and sixth transmembrane domains of G protein-coupled receptor superfamily, were used for the polymerase chain reaction amplification and consecutive characterization of G protein-coupled receptors present in cultured rabbit aortic smooth muscle cells. One of the isolated resulting fragments was highly homologous to the corresponding region of the bradykinin (BK) B2 receptor cloned in other species. The polymerase chain reaction fragment was used to screen a rabbit genomic library, which allowed the identification of an intronless 1101-nucleotide open reading frame which codes for a 367-amino acid receptor protein. The rabbit B2 receptor sequence is more than 80% identical to the ones determined in three other species and retain putative glycosylation, palmitoylation and phosphorylation sites. In the rabbit genomic sequence, an acceptor splice sequence was found 8 base pairs upstream of the start codon. Northern blot analysis showed a high expression of a major transcript (4.2 kilobases) in the rabbit kidney and duodenum, and a less abundant expression in other tissues. Southern blot experiments suggest that a single copy of this gene exists in the rabbit genome. The cloned rabbit B2 receptor expressed in COS-1 cells binds [3H]BK in a saturable manner (KD 2.1 nM) and this ligand competes with a series of kinin agonists and antagonist with a rank order consistent with the B2 receptor identity. The insurmountable character of the antagonism exerted by Hoe 140 against BK on the rabbit B2 receptor, previously shown in pharmacological experiments, was confirmed in binding experiments with the cloned receptor expressed in a controlled manner. By contrast, Hoe 140 competed with [3H]BK in a surmountable manner for the human B2 receptor expressed in COS-1 cells. The cloning of the rabbit B2 receptor will be useful notably for the study of the structural basis of antagonist binding and for studies on receptor regulation in a relatively large animal.

Aortic arch syndrome

MedlinePlus

... including: Congenital absence of a branch of the aorta Isolation of the subclavian arteries Vascular rings An ... Braverman AC. Diseases of the aorta. In: Bonow RO, Mann DL, Zipes DP, ... Heart Disease: A Textbook of Cardiovascular Medicine . 10th ...

Protective effect of melatonin on experimental spinal cord ischemia.

PubMed

Erten, S F; Kocak, A; Ozdemir, I; Aydemir, S; Colak, A; Reeder, B S

2003-10-01

Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta. To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia-reperfusion (IR) injury. Medical Biology Laboratory, Inonu University, Malatya, Turkey. Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities. Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre- or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia-reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group. To our knowledge, this is the first study that shows the effects of melatonin administered both pre- and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.

Vasomodulatory effect of novel peroxovanadate compounds on rat aorta: Role of rho kinase and nitric oxide/cGMP pathway.

PubMed

Khanna, Vivek; Jain, Manish; Barthwal, Manoj Kumar; Kalita, Diganta; Boruah, Jeena Jyoti; Das, Siva Prasad; Islam, Nashreen S; Ramasarma, Tangirala; Dikshit, Madhu

2011-09-01

The present study was undertaken to assess the role of reactive oxygen species (ROS) in rat aortic ring vasoreactivity and integrity by using various peroxovanadate (pV) compounds. All the pV compounds (1nM-300 μM) used in the present study exerted concentration-dependent contractions on endothelium intact rat aortic rings. All compounds with an exception of DPV-asparagine (DPV-asn) significantly altered vascular integrity as shown by diminished KCl responses. Phenylephrine (PE)-mediated contractions (3nM-300 μM) were unaltered in the presence of these compounds. Acetylcholine (Ach)-mediated relaxation in PE (1μM) pre-contracted rings was significantly reduced in presence of diperoxovanadate (DPV), poly (sodium styrene sulfonate-co-maleate)-pV (PSS-CoM-pV) and poly (sodium styrene 4-sulfonate)-pV (PSS-pV). However, no significant change in Ach-mediated responses was observed in the presence of poly (acrylate)-pV (PAA-pV) and DPV-asn. DPV-asn was thus chosen to further elucidate mechanism involved in peroxide mediated modulation of vasoreactivity. DPV-asn (30nM - 300 μM) exerted significantly more stable contractions, that was found to be catalase (100U/ml) resistant in comparison with H(2)O(2) (30nM-300 μM) in endothelium intact aortic rings. These contractile responses were found to be dependent on extracellular Ca(2+) and were significantly inhibited in presence of ROS scavenger N-acetylcysteine (100 μM). Intracellular calcium chelation by BAPTA-AM (10μM) had no significant effect on DPV-asn (30nM-300 μM) mediated contraction. Pretreatment of aortic rings by rho-kinase inhibitor Y-27632 (10μM) significantly inhibited DPV-asn-mediated vasoconstriction indicating role of voltage-dependent Ca(2+) influx and downstream activation of rho-kinase. The small initial relaxant effect obtained on addition of DPV-asn (30nM-1 μM) in PE (1 μM) pre-contracted endothelium intact rings, was prevented in the presence of guanylate cyclase inhibitor, methylene blue (10 μM) and/or nitric oxide synthase (NOS) inhibitor, l-NAME (100 μM) suggesting involvement of nitric oxide and cGMP. DPV-asn, like H(2)O(2), exerted a response of vasoconstriction in normal arteries and vasodilation at low concentrations (30nM-1 μM) in PE-pre contracted rings with overlapping mechanisms. These findings suggest usefulness of DPV-asn having low toxicity, in exploring the peroxide-mediated effects on various vascular beds. The present study also convincingly demonstrates role of H(2)O(2) in the modulation of vasoreactivity by using stable peroxide DPV-asn and warrants future studies on peroxide mediated signaling from a newer perspective. 2011 Published by Elsevier Ltd.

A new image-based process for quantifying hemodynamic contributions to long-term morbidity in a rabbit model of aortic coarctation

NASA Astrophysics Data System (ADS)

Wendell, David C.; Dholakia, Ronak J.; Larsen, Paul M.; Menon, Arjun; LaDisa, John F., Jr.

2010-03-01

Coarctation of the aorta (CoA) is associated with reduced life expectancy despite successful surgical treatment. Interestingly, much of the related long-term morbidity can be explained by abnormal hemodynamics, vascular biomechanics and cardiac function. MRI has played an important role in assessing coarctation severity, but the heterogeneity and small number of patients at each center presents an obstacle for determining causality. This work describes optimized imaging parameters to create computational fluid dynamics (CFD) models revealing changes in hemodynamics and vascular biomechanics from a rabbit model. CoA was induced surgically at 10 weeks using silk or dissolvable ligatures to replicate native and end-to-end treatment cases, respectively. Cardiac function was evaluated at 32 weeks using a fastcard SPGR sequence in 6-8 two-chamber short-axis views. Left ventricular (LV) volume, ejection fraction, and mass were quantified and compared to control rabbits. Phase contrast (PC) and angiographic MRI were used to create CFD models. Ascending aortic PCMRI data were mapped to the model inflow and outflow boundary conditions replicated measured pressure (BP) and flow. CFD simulations were performed using a stabilized finite element method to calculate indices including velocity, BP and wall shear stress (WSS). CoA models displayed higher velocity through the coarctation region and decreased velocity elsewhere, leading to decreased WSS above and below the stenosis. Pronounced wall displacement was associated with CoA-induced changes in BP. CoA caused reversible LV hypertrophy. Cardiac function was maintained, but caused a persistent hyperdynamic state. This model may now be used to investigate potential mechanisms of long-term morbidity.

Vasodilator effects and putative guanylyl cyclase stimulation by 2-nitro-1-phenylethanone and 2-nitro-2-phenyl-propane-1,3-diol on rat aorta.

PubMed

Vasconcelos, Thiago Brasileiro de; Ribeiro-Filho, Helder Veras; Lahlou, Saad; Pereira, José Geraldo de Carvalho; Oliveira, Paulo Sérgio Lopes de; Magalhães, Pedro Jorge Caldas

2018-07-05

Compounds containing a nitro group may reveal vasodilator properties. Several nitro compounds have a NO 2 group in a short aliphatic chain connected to an aromatic group. In this study, we evaluated in rat aorta the effects of two nitro compounds, with emphasis on a putative recruitment of the soluble guanylate cyclase (sGC) pathway to induce vasodilation. Isolated aortic rings were obtained from male Wistar rats to compare the effects induced by 2-nitro-1-phenylethanone (NPeth) or 2-nitro-2-phenyl-propane-1,3-diol (NPprop). In aortic preparations contracted with phenylephrine or KCl, NPeth and NPprop induced vasorelaxant effects that did not depend on the integrity of vascular endothelium. NPeth had a lesser vasorelaxant efficacy than NPprop and only the NPprop effects were inhibited by pretreatment with the sGC inhibitors, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue. In an ODQ-preventable manner, NPprop inhibited the contractile component of the phenylephrine-induced response mediated by intracellular Ca 2+ release or by extracellular Ca 2+ recruitment through receptor- or voltage-operated Ca 2+ channels. In contrast, NPprop was inert against the transient contraction induced by caffeine in Ca 2+ -free medium. In an ODQ-dependent manner, NPprop inhibited the contraction induced by the protein kinase C activator phorbol 12,13-dibutyrate or by the tyrosine phosphatase inhibitor sodium orthovanadate. In silico docking analysis of a sGC homologous protein revealed preferential site for NPprop. In conclusion, the nitro compounds NPeth and NPprop induced vasorelaxation in rat aortic rings. Aliphatic chain substituents selectively interfered in the ability of these compounds to induce vasorelaxant effects, and only NPprop relaxed aortic rings via a sGC pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Double aortic arch and persistent left vena cava in a white lion cub (Panthera leo).

PubMed

Goldin, J P; Lambrechts, N E

1999-03-01

A 4-mo-old female white lion (Panthera leo) cub was presented with a 2-wk history of persistent postprandial regurgitation, mild dyspnea, and poor weight gain. The cub was weak and thin but otherwise alert. Survey and contrast radiography revealed a large dilated esophagus cranial to the heart base, with an esophageal filling defect present at the level of the fourth thoracic vertebra. A vascular ring anomaly was tentatively diagnosed. Exploratory thoracotomy revealed a double aortic arch and a persistent left vena cava. The left aortic arch was ligated and divided, and recovery was uneventful. A single episode of regurgitation occurred within the first postoperative month, and the cub gained 5.5 kg in weight during the same time period. Neither double aortic arch nor persistent left vena cava has been reported in a nondomestic felid.

Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine.

PubMed

Schott, C A; Gray, G A; Stoclet, J C

1993-01-01

1. The dependence on extracellular L-arginine of vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) was studied in vivo in rats infused with LPS and in vitro in endothelium-denuded rat thoracic aortic rings exposed to LPS. 2. Infusion of LPS during 50 min at a dose of 10 mg kg-1 h-1 produced a significant impairment of the pressor effect of noradrenaline, while in tissues collected 60 min after the start of LPS infusion, no significant alteration in either plasma arginine concentration or aortic arginine content was found compared to saline-infused controls (where plasma arginine was 78.5 +/- 7 microM and aortic arginine 394 +/- 124 nmol g-1 tissue). 3. Incubation of isolated, endothelium-denuded aortic rings with LPS (10 micrograms ml-1) in the absence of L-arginine for 4 h at 37 degrees C produced a 6 fold (P < 0.01) rightward shift in the noradrenaline concentration-effect curve compared to polymyxin B (1 micrograms ml-1, a LPS neutralizing agent) and reduced by 15% the maximum observed tension. 4. The presence of L-arginine (100 microM) during the incubation with LPS and throughout the following contraction experiments caused a 15 fold (P < 0.01) increase in the EC50 of noradrenaline and greater depression (45%) of the maximum observed tension compared to polymyxin B-treated controls. Responses in control, non LPS-treated rings were unaffected by the presence of L-arginine. 5. The addition of L-arginine to rings incubated with LPS in the absence of L-arginine and maximally precontracted with noradrenaline (10 microM) induced a dose-dependent relaxation. The EC50 of L-arginine was 8.0+/-0.3mu.6. The reactivity of LPS-treated rings to noradrenaline both in the absence and presence of L-arginine was restored to control levels by N0-nitro-L-arginine methyl ester (L-NAME, 300 mu), an inhibitor of NO production and by methylene blue (3 JAM), an inhibitor of guanylate cyclase.7. Incubation of isolated aortae in the absence of L-arginine did not significantly decrease the tissue arginine content, whether LPS (10 fg ml-') was present or not. Similarly, the presence of L-arginine(100 mu) in the incubation medium did not modify the tissue arginine content.8. These results show that the LPS-induced impairment of vasoconstriction elicited by noradrenaline is dependent on extracellular L-arginine, although the tissue arginine content is not depleted after LPS pretreatment, and that circulating L-arginine is sufficient to activate maximally the vascular L-arginine/NO pathway in endotoxaemic rats.

Carob pod insoluble fiber exerts anti-atherosclerotic effects in rabbits through sirtuin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α.

PubMed

Valero-Muñoz, María; Martín-Fernández, Beatriz; Ballesteros, Sandra; Lahera, Vicente; de las Heras, Natalia

2014-09-01

The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g ⋅ kg(-1) ⋅ d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g ⋅ kg(-1) ⋅ d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-β (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of SIRT1 and PGC-1α (160% and 121% of the control group, respectively; P < 0.05) vascular expression. In summary, we demonstrated for the first time, to our knowledge, that administration of IFC reduces the development of atherosclerosis in rabbits. This effect seems to be related to an improvement in endothelial function and a reduction of inflammation and fibrosis, most probably as a consequence of the reduction of serum concentrations of cholesterol and triglycerides. Increased expression of aortic SIRT1 and PGC-1α could play an important role in the observed effects of IFC in rabbits with dyslipidemia. © 2014 American Society for Nutrition.

Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice

PubMed Central

Trapeaux, J; Busseuil, D; Shi, Y; Nobari, S; Shustik, D; Mecteau, M; El-Hamamsy, I; Lebel, M; Mongrain, R; Rhéaume, E; Tardif, J-C

2013-01-01

Background and Purpose We have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS. Experimental Approach Apolipoprotein E-deficient (ApoE−/−) mice and mice with Werner progeria gene deletion (WrnΔhel/Δhel) received high-fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA-I mimetic peptide infusions (ApoA-I treated groups, 100 mg·kg−1 for ApoE−/− mice; 50 mg·kg−1 for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology. Key Results Aortic valve area (AVA) increased in both ApoE−/− and Wrn mice treated with the ApoA-I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA-I treated ApoE−/− mice. The type I/III collagen ratio was lower in the sinus wall of ApoA-I treated ApoE−/− mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA-I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA. Conclusions and Implications ApoA-I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice. PMID:23638718

Transplantation of rib cartilage reshaped with 1.56 μm laser radiation in rabbits

NASA Astrophysics Data System (ADS)

Sobol, E.; Baum, O.; Alexandrovskaya, Yu.; Shekhter, A.; Selezneva, L.; Svistuskin, V.

2017-02-01

As cartilage is an ideal natural material for transplantation, its use in the ENT surgery is limited by a difficulty to get proper shape of cartilage implants. Aim of the work is to make ring-shaped cartilage implants, to check their stability after laser reshaping and to perform transplantation into rabbits in vivo. We experimented with costal cartilages of 1-2 mm in thickness obtained from 3rd and 4rd ribs of a rabbit. 1.56 μm laser (Arcuo Medical Inc.) was used for cartilage reshaping. The laser settings were established taking into account anisotropy of cartilage structure for different orientation of the implants. The reshaped cartilage implants were surgically sewn to rib cartilages of the other rabbits. The rabbits were slaughtered in 3.5-4 months after surgery. The results have shown that (1) all reshaped implants kept circular form, and (2) the implants were adhered to the native rabbit cartilage sites (3) pronounced signs of regeneration in the intermediate zones were observed. The prospects of the cartilage implants use in larynx stenosis surgery are discussed.

Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

PubMed

Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

2018-01-20

Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  < 22 μM) than that of the reference compound diazoxide (EC 50  = 24 μM). Interestingly, several tested compounds of series B also presented stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50  < 10 μM). By contrast, series A derivatives were poorly active on aortic rings (EC 50  > 57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

PubMed Central

Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

2002-01-01

We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

The thrombin inhibitor argatroban does not influence the endothelium-dependent relaxant and contractile responses of isolated rabbit carotid arteries.

PubMed

Schrödter, Hans-Martin; Glusa, Erika

2003-06-01

Atherosclerotic endothelial dysfunctions are associated with a reduced NO production, which is probably due to impaired NO synthase (eNOS) activity or a deficiency of the substrate L-arginine. In the present studies, the influence of argatroban on isolated rabbit carotid arteries was investigated to determine whether the arginine derivative argatroban can improve the endothelium-dependent relaxation. Rings from rabbit carotid arteries were placed in 10 ml organ baths for isometric tension recording. Endothelial integrity was assessed by the acetylcholine-induced relaxation of PGF2alpha-precontracted rings; after mechanical removal of the endothelium the relaxation was abolished. Preincubation of the vessels in vitro with L-NAME, an inhibitor of the eNOS, diminished significantly the acetylcholine-induced relaxation by more than 50%. After i.v. application of L-NAME (100 mg/kg) in rabbits, relaxation in response to acetylcholine was significantly reduced compared to the control when the vessels were studied ex vivo in an organ bath. The contractile effects of phenylephrine and 5-HT were slightly enhanced. Argatroban is a selective, potent, synthetic thrombin inhibitor; after i.v. application at doses of 0.5 and 1.0 mg/kg, a significant prolongation of the plasma coagulation time (measured as thrombin time and a PTT) of up to 60 min was found in rabbits. In vitro argatroban did not affect the acetylcholine-induced relaxation or the contractile response to phenylephrine and 5-HT. After i.v. application, the ex vivo experiments in the organ bath showed that after 30 min the relaxant responses of the carotid arteries to acetylcholine and the contractile effects of phenylephrine and 5-HT were not influenced by pretreatment with argatroban. The present studies suggest that argatroban has no vascular effects in vitro and ex vivo in normal rabbits.

Absence of ligand-induced regulation of kinin receptor expression in the rabbit

PubMed Central

Sabourin, Thierry; Guay, Katline; Houle, Steeve; Bouthillier, Johanne; Bachvarov, Dimcho R; Adam, Albert; Marceau, François

2001-01-01

The induction of B1 receptors (B1Rs) and desensitization or down-regulation of B2 receptors (B2Rs) as a consequence of the production of endogenous kinins has been termed the autoregulation hypothesis. The latter was investigated using two models based on the rabbit: kinin stimulation of cultured vascular smooth muscle cells (SMCs) and in vivo contact system activation (dextran sulphate intravenous injection, 2 mg kg−1, 5 h).Rabbit aortic SMCs express a baseline population of B1Rs that was up-regulated upon interleukin-1β treatment ([3H]-Lys-des-Arg9-BK binding or mRNA concentration evaluated by RT–PCR; 4 or 3 h, respectively). Treatment with B1R or B2R agonists failed to alter B1R expression under the same conditions.Despite consuming endogenous kininogen (assessed using the kinetics of immunoreactive kinin formation in the plasma exposed to glass beads ex vivo) and producing hypotension mediated by B2Rs in anaesthetized rabbits, dextran sulphate treatment failed to induce B1Rs in conscious animals (RT–PCR in several organs, aortic contractility). By contrast, lipopolysaccharide (LPS, 50 μg kg−1, 5 h) was an effective B1R inducer (kidney, duodenum, aorta) but did not reduce kininogen reserve.We tested the alternate hypothesis that endogenous kinin participate in LPS induction of B1Rs. Kinin receptor antagonists (icatibant combined to B-9858, 50 μg kg−1 of each) failed to prevent or reduce the effect of LPS on B1R expression. Dextran sulphate or LPS treatments did not persistently down-regulate vascular B2Rs (jugular vein contractility assessed ex vivo).The kinin receptor autoregulation hypothesis is not applicable to primary cell cultures derived from a tissue known to express B1Rs in a regulated manner (aorta). The activation of the endogenous kallikrein-kinin system is ineffective to induce B1Rs in vivo in an experimental time frame sufficient for B1R induction by LPS. PMID:11487527

Measuring ocular characteristics after gel injection adjustable keratoplasty (GIAK) in the rabbit

NASA Astrophysics Data System (ADS)

Comander, Jason I.; Parel, Jean-Marie A.; Simon, Gabriel; Takesue, Yoshiko; Villain, Franck L.

1995-05-01

Gel Injection Adjustable Keratoplasty (GIAK) is a refractive surgery procedure which uses an ocular ring implant made of a polyethylene oxide hydrogel to cause a refractive change in the cornea. Unlike laser photo refractive keratectomy, GIAK does not interfere with the central cornea because the ring lies around the optical axis. Thus, vision can be assessed immediately after surgery. Our in vivo study was designed to quantify GIAK's effects on tissues, the biocompatibility of the polymer and in the process investigate which ocular changes in the rabbit model can be monitored with precision using current technology. Thirty-two young rabbits underwent a delamination in one eye, 22 of which were injected with a new polymeric gel. Corneal topography, keratometry, pachymetry, and tonometry were performed on both eyes for up to 105 days. All corneas flattened with growth. In GIAK animals, we found an average flattening of 6.51 +/- 1.23 diopters (p < 0.0001) relative to the fellow eye. No statistically significant regression over the 102 days was observed. Intraocular pressure dropped slightly by 0.69 +/- 1.21 mmHg (p equals 0.025), a clinically insignificant value, while no significant change was detected in corneal thickness. Keratometry can be tracked in rabbits after GIAK surgery from POD 1. Measuring unoperated fellow eyes allows for the effects of surgery to be assessed without bias from growth. Using this protocol, GIAK was shown to be stable. It was more difficult to draw conclusions from pachymetry, tonometry, and topography data.

Thiopental inhibits nitric oxide production in rat aorta.

PubMed

Castillo, C; Asbun, J; Escalante, B; Villalón, C M; López, P; Castillo, E F

1999-12-01

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.

Cardiovascular effects of Urtica dioica L. (Urticaceae) roots extracts: in vitro and in vivo pharmacological studies.

PubMed

Testai, Lara; Chericoni, Silvio; Calderone, Vincenzo; Nencioni, Giulia; Nieri, Paola; Morelli, Ivano; Martinotti, Enrica

2002-06-01

Urtica dioica (Urticaceae) is a plant principally used in the traditional medicine of oriental Marocco as antihypertensive remedy (J. Ethnopharmacol., 58 (1997), 45). The aim of this work was to evaluate a possible direct cardiovascular action of the plant and to investigate its mechanism of action. In aortic preparations with intact and functional endothelial layer, pre-contracted with KCl 20 mM or norepinephrine 3 microM, the crude aqueous and methanolic extracts of the plant roots, as well as purified fractions elicited a vasodilator action. Nevertheless, the vasodilator activity was not present in aortic rings without endothelial layer. In aortic rings with intact endothelial layer, the vasorelaxing effect was abolished by L-NAME, a NO-biosynthesis inhibitor, and ODQ, a guanylate cyclase inhibitor. Furthermore, potassium channel blockers (TEA, 4-aminopyridine, quinine, but not glybenclamide) antagonized the vasodilator action of the purified fraction F1W of U. dioica. The same fraction produced a marked decrease of inotropic activity, in spontaneously beating atria of guinea-pig, and a marked, but transient, hypotensive activity on the blood pressure of anaesthetized rats. It is concluded that U. dioica can produce hypotensive responses, through a vasorelaxing effect mediated by the release of endothelial nitric oxide and the opening of potassium channels, and through a negative inotropic action.

External heating of stents by radio waves Pilot studies in rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitt, Adam B.; Robinson, Keith; Chronos, Nicolas A.F.

Purpose: This experiment was designed to assess the feasibility of radio frequency energy delivered by a prototype radio frequency generator inductive heating device (REVAX) positioned external to the body, for transient heating of stents after arterial implant. Methods and Materials: Twenty-one New Zealand White rabbits underwent stenting of their infrarenal aorta. Nine rabbits were stented and immediately placed in the REVAX for external stent heating with internal temperature probes in place. Twelve rabbits were stented and 3 days later either heated or placed in the generator as a sham for 20 min. The animals were terminated 28 days later. Results:more » The REVAX was able to heat the aortic stents in a controlled fashion; in Phase II experiments, the stent temperature was raised to 42 deg. C for 20 min. In Phase I mild necrosis was noted at the stent struts. In Phase II, necrosis and mineralization of the media was seen at the stent struts, and evidence of neointimal suppression was observed. Conclusion: This study demonstrated that external heating of stents in a blood vessel in a live animal via radio frequency energy is feasible. Further studies will be needed to assess whether any specific heating regimen might inhibit fibrocellular neointimal hyperplasia.« less

Experimental Candida albicans endocarditis: characterization of the disease and response to therapy.

PubMed Central

Sande, M A; Bowman, C R; Calderone, R A

1977-01-01

Endocarditis caused by Candida albicans was induced in rabbits after insertion of a catheter across the aortic valve. The mean survival time of 34 rabbits was 26 days. Only 7% of temperature recordings taken were elevated. Candida was recovered from only 9% of blood cultures taken. Precipitating and agglutinating serum antibody was detected after 12 days of infection. Antibody titers rose progressively until death in rabbits with endocarditis, whereas titers peaked early and subsequently decreased in animals that received an intravenous injection of C. albicans without precatheterization. Three groups of rabbits were treated for 6 days with amphotericin B, 5-fluorocytosine, or the two durgs in combination. Amphotericin B alone reduced the mean titer of organisms from log10 8.79 +/- 1.46 to log 10 3.1 +/- 1.9 colony-forming units/g. 5-Fluorocytosine was less effective (mean titer after 6 days of therapy was log10 7.4 +/- 0.33 colony-forming units/g). The addition of 5-fluorocytosine to amphotericin B did not increase the rate at which Candida cells were eradicated from the vegetations. These in vivo results corrleated with the failure to demonstrate an increased rate of fungicidal activity in vitro with the two drugs. Images PMID:328393

SUBCOMMISSURAL IMPLANTATION OF AORTIC PROSTHESES WITH THE USE OF THE NONCORONARY SINUS AND THE FIBROUS TRIGONES

PubMed Central

Liotta, Domingo; Haller, Jordan D.; Pisanu, Amadeo; Bracco, Daniel; Bertolozzi, Enrique

1979-01-01

The technique described here permits insertion of a large prosthesis into a small aortic annulus and avoids the necessity of additional procedures for enlarging the aortic ring. Inspection of the fibrous skeleton of the heart reveals that the large intervalvular trigone and the noncoronary sinus of Valsalva are remarkably elastic. Full advantage of this natural elasticity is achieved by suturing the prosthesis to the base of these structures from outside the aorta. Sutures are placed in the sinuses of the right and left cusps in the usual manner. Judicious application of this procedure allows the implantation of a No. 23 or No. 24 prosthesis in cases that would require a No. 19 or No. 21 with the use of conventional methods. Images PMID:15216322

Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-α glycyrrhetinic acid

PubMed Central

Taylor, Hannah J; Chaytor, Andrew T; Evans, W Howard; Griffith, Tudor M

1998-01-01

The gap junction inhibitor 18-α-glycyrrhetinic acid (α-GA, 100 μM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by ∼20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 300 μM) inhibited relaxations to both agents by ∼65% and these were further attenuated by α-GA to <10% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not affected by α-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery. PMID:9776336

Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries in vitro and increased optic disc blood flow in vivo.

PubMed

Chuman, Hideki; Sugimoto, Takako; Nao-I, Nobuhisa

2017-12-01

This study aimed to clarify the vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate changes in optic disc blood flow after an infusion of L-arginine in vivo. Vascular ring segments were mounted on a double myograph system. After obtaining maximal contraction following administration of high-K solution, L-arginine was administrated. Six volunteers received an intravenous drip infusion of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured by laser speckle flowgraphy. L-arginine relaxed high-K solution-induced contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs. After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide production. In the L-arginine infusion group, the mean blur rate was significantly greater than that of the control group in vivo. L-arginine has both nitric oxide-dependent and independent vasodilatory effect on high K- induced contractions in isolated rabbit and human PCAs. L-arginine increased optic disc blood flow in vivo.

Rabbits with naturally occurring cataracts referred for phacoemulsification and intraocular lens implantation: a preliminary study of 12 cases.

PubMed

Sanchez, Rick F; Everson, Richard; Hedley, Joanna; Dawson, Charlotte; Lam, Richard; Priestnall, Simon L; Garcia de Carellan, Alejandra; de Miguel, Cristina; Seymour, Christopher

2017-12-04

To describe the presentation of 15 rabbits with naturally occurring cataracts referred for phacoemulsification surgery, the procedure in 13 cases and the follow-up in 12. Fifteen rabbits (30 eyes), nine of which stopped following visual cues in association with cataract progression. Rabbits underwent preoperative ophthalmic and ocular ultrasound examination. Thirteen rabbits (22 eyes) had mature cataracts. Ten were bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The cataract in one of these was incipient. One rabbit had bilateral immature cataracts. One rabbit had a subluxated lens, and one had a retinal detachment. Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet ® , Berlin, Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D 20S-models. Intraoperative complications included one unilateral posterior-capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One rabbit died during anesthetic recovery. Nine cases were PCR-tested for Encephalitozoon cuniculi, and only three were positive. The median follow-up time was 12 months (4-24 months). Rabbits that were not following visual cues preoperatively did so postoperatively, and surgery resulted in a clear visual axis for the follow-up period in every case except in two, due to reasons other than the surgery. Phacoemulsification with CTR and IOL implantation offers good long-term results and can improve the quality of life of pet rabbits. Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic death are potential complications. © 2017 American College of Veterinary Ophthalmologists.

Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.

PubMed

Sugano, M; Makino, N; Sawada, S; Otsuka, S; Watanabe, M; Okamoto, H; Kamada, M; Mizushima, A

1998-02-27

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits.

Experimental study on oral sulfhydryl as an adjuvant for improving nitrate ester tolerance in an animal model.

PubMed

Chen, L; Jiang, J-Q; Zhang, Y; Feng, H

2018-03-01

As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed. After feeding the animals for 5 days, the concentrations of superoxide anion (•O2-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in blood and the relaxation response of the aortic ring were determined in each subject. The vascular plaques in different treatment groups were assessed by Hematoxylin and eosin (HE) staining to investigate the therapeutic value of sulfhydryl as coadjuvant for improving nitrate ester tolerance, and changes in blood vessels in different treatment groups were studied by immunohistochemical assays. Our results showed no significant differences through time in the concentrations of •O2-, SOD, MDA, NO, ET-1 between the healthy control and the nitrate ester groups (p > 0.05). The levels of SOD and MDA in the nitrate ester tolerance group increased with time, however, the levels of •O2-, NO and ET-1 decreased gradually (p < 0.05). The NO, •O2- and ET-1 levels in both the AS and AS + nitrate ester tolerance groups were significantly decreased, but SOD and MDA were significantly increased (p < 0.05). SOD and MDA in the AS + nitrate ester group decreased gradually with time, but •O2-, NO- and ET-1 levels increased (p < 0.05). The levels of SOD and MDA in the AS + drug combination and the drug combination group decreased significantly with time, in contrast, those of •O2-, NO- and ET-1 increased (p < 0.05). The results of HE staining proved that the atherosclerosis model was established successfully. We conclude the use of a sulfhydryl compound as an adjuvant significantly reduced nitrate ester tolerance, and this strategy was safe and looks promising for humans.

Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta

PubMed Central

Jiménez, Rosario; Andriambeloson, Emile; Duarte, Juan; Andriantsitohaina, Ramaroson; Jiménez, José; Pérez-Vizcaino, Francisco; Zarzuelo, Antonio; Tamargo, Juan

1999-01-01

The present study was undertaken to analyse the mechanism of the contractile response induced by the bioflavonoid myricetin in isolated rat aortic rings.Myricetin induced endothelium-dependent contractile responses (maximal value=21±2% of the response induced by 80 mM KCl and pD2=5.12±0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively.Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 μM), the cyclo-oxygenase inhibitor, indomethacin (10 μM), the thromboxane synthase inhibitor, dazoxiben (100 μM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 μM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 μM).In cultured bovine endothelial cells (BAEC), myricetin (50 μM) produced an increase in cytosolic free calcium ([Ca2+]i) which peaked within 1 min and remained sustained for 6 min, as determined by the fluorescent probe fura 2. This rise in [Ca2+]i was abolished after removal of extracellular Ca2+ in the medium.Myricetin (50 μM) significantly increased TXB2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca2+-free media and by indomethacin.Taken together, these results suggests that myricetin stimulates Ca2+ influx and subsequently triggers the activation of the PLA2 and cyclo-oxygenase pathways releasing TXA2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of Tp receptors on vascular smooth muscle cells. PMID:10455307

Metformin exaggerates phenylephrine-induced AMPK phosphorylation independent of CaMKKβ and attenuates contractile response in endothelium-denuded rat aorta

PubMed Central

Pyla, Rajkumar; Osman, Islam; Pichavaram, Prahalathan; Hansen, Paul; Segar, Lakshman

2014-01-01

Metformin, a widely prescribed antidiabetic drug, has been shown to reduce the risk of cardiovascular disease, including hypertension. Its beneficial effect toward improved vasodilation results from its ability to activate AMPK and enhance nitric oxide formation in the endothelium. To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists. In the present study, ex vivo incubation of endothelium-denuded rat aortic rings with 3 mM metformin for 2 hours resulted in significant accumulation of metformin (~600 pmoles/mg tissue), as revealed by LC-MS/MS MRM analysis. However, metformin did not show significant increase in AMPK phosphorylation under these conditions. Exposure of aortic rings to a GPCR agonist (e.g., phenylephrine) resulted in enhanced AMPK phosphorylation by ~2.5-fold. Importantly, in metformin-treated aortic rings, phenylephrine challenge showed an exaggerated increase in AMPK phosphorylation by ~9.7-fold, which was associated with an increase in AMP/ATP ratio. Pretreatment with compound C (AMPK inhibitor) prevented AMPK phosphorylation induced by phenylephrine alone and also that induced by phenylephrine after metformin treatment. However, pretreatment with STO-609 (CaMKKβ inhibitor) diminished AMPK phosphorylation induced by phenylephrine alone but not that induced by phenylephrine after metformin treatment. Furthermore, attenuation of phenylephrine-induced contraction (observed after metformin treatment) was prevented by AMPK inhibition but not by CaMKKβ inhibition. Together, these findings suggest that, upon endothelial damage in the vessel wall, metformin uptake by the underlying vascular smooth muscle would accentuate AMPK phosphorylation by GPCR agonists independent of CaMKKβ to promote vasorelaxation. PMID:25179145

MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor

PubMed Central

Aragon, Mario; Erdely, Aaron; Bishop, Lindsey; Salmen, Rebecca; Weaver, John; Liu, Jim; Hall, Pamela; Eye, Tracy; Kodali, Vamsi; Zeidler-Erdely, Patti; Stafflinger, Jillian E.; Ottens, Andrew K.; Campen, Matthew J.

2016-01-01

Inhalation of multiwalled carbon nanotubes (MWCNT) causes systemic effects including vascular inflammation, endothelial dysfunction, and acute phase protein expression. MWCNTs translocate only minimally beyond the lungs, thus cardiovascular effects thereof may be caused by generation of secondary biomolecular factors from MWCNT-pulmonary interactions that spill over into the systemic circulation. Therefore, we hypothesized that induced matrix metalloproteinase-9 (MMP-9) is a generator of factors that, in turn, drive vascular effects through ligand-receptor interactions with the multiligand pattern recognition receptor, CD36. To test this, wildtype (WT; C57BL/6) and MMP-9−/− mice were exposed to varying doses (10 or 40 µg) of MWCNTs via oropharyngeal aspiration and serum was collected at 4 and 24 h postexposure. Endothelial cells treated with serum from MWCNT-exposed WT mice exhibited significantly reduced nitric oxide (NO) generation, as measured by electron paramagnetic resonance, an effect that was independent of NO scavenging. Serum from MWCNT-exposed WT mice inhibited acetylcholine (ACh)-mediated relaxation of aortic rings at both time points. Absence of CD36 on the aortic rings (obtained from CD36-deficient mice) abolished the serum-induced impairment of vasorelaxation. MWCNT exposure induced MMP-9 protein levels in both bronchoalveolar lavage and whole lung lysates. Serum from MMP-9−/− mice exposed to MWCNT did not diminish the magnitude of vasorelaxation in naïve WT aortic rings, although a modest right shift of the ACh dose–response curve was observed in both MWCNT dose groups relative to controls. In conclusion, pulmonary exposure to MWCNT leads to elevated MMP-9 levels and MMP-9-dependent generation of circulating bioactive factors that promote endothelial dysfunction and decreased NO bioavailability via interaction with vascular CD36. PMID:26801584

Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H₂S pathway.

PubMed

Horrigan, Louise A; Holohan, Catherine A; Lawless, Gráinne A; Murtagh, Melissa A; Williams, Carmel T; Webster, Christina M

2013-02-26

The objective of this study was to investigate the in vitro effects of blueberry juice on healthy rat aortic rings, and to explore the roles of potassium channels and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of blueberry juice. Firstly, the antioxidant capacity of blueberry juice was compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH assays. Blueberry juice had significantly higher total polyphenol content than any of the other drinks studied (p < 0.01). The effect of blueberry juice on noradrenaline-contracted aortic rings was then observed, and the juice caused significant inhibition of noradrenaline-induced contractions (p < 0.01). Voltage-gated potassium channel (Kv) blockers 4-aminopyridine (1 mM) and 3,4-diaminopyridine (1 mM), as well as the cystathionine γ-lysase (CSE) inhibitor d,l-propargylglycine (2 mM) were then utilised to elucidate the role of Kv channels and the CSE/H(2)S pathway. Kv channel blocker 3,4-diaminopyridine caused significant blockade at 1/100 and 1/50 dilutions of juice (p < 0.01), whilst 4-aminopyridine caused significant blockade of the 1/100 dilution of blueberry juice (p < 0.05). In addition, d,l-propargylglycine potently inhibited the effect of 1/100 and 1/50 dilutions of blueberry juice (p < 0.01). This study indicates that blueberry juice has potent vasorelaxing properties, and thus may be a useful dietary agent for the prevention and treatment of hypertension. This study also provides strong evidence that Kv channels and the CSE/H(2)S pathway may be responsible, at least in part, for mediating the effects of blueberry juice.

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

PubMed Central

Vatanabe, Izabela Pereira; Rodrigues, Carla Nascimento dos Santos; Buzinari, Tereza Cristina; de Moraes, Thiago Francisco; da Silva, Roberto Santana; Rodrigues, Gerson Jhonatan

2017-01-01

Background The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Objective Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Methods Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. Results In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Conclusion Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats. PMID:28678930

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea.

PubMed

García-Arredondo, Alejandro; Rojas-Molina, Alejandra; Ibarra-Alvarado, César; Lazcano-Pérez, Fernando; Arreguín-Espinosa, Roberto; Sánchez-Rodríguez, Judith

2016-01-01

Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa , Porites astreoides and Siderastrea siderea , three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A 2 (PLA 2 ), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A 2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits

PubMed Central

2010-01-01

Background Piper sarmentosum (P.s) has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically. Aim The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits. Methods Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study. Results Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 ± 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 ± 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups. Conclusion Administration of P.s extract has protective effect against atheroscleros PMID:20433693

Respiratory failure and lethal hypotension due to blue-ringed octopus and tetrodotoxin envenomation observed and counteracted in animal models.

PubMed

Flachsenberger, W A

The effects of crude blue-ringed octopus venom gland extract and tetrodotoxin (TTX) on anaesthetised rats and rabbits were studied. Paralysis of the respiratory musculature causing anoxia and cyanosis was overcome with positive, artificial respiration. The second lethal mechanism of the toxins: rapid and severe hypotension, had to be counteracted peripherally, since neural transmission had been drastically reduced by the toxins. Noradrenaline, d-amphetamine, phenylephrine and methoxamine, agonists acting on vascular adrenergic a-receptors, were tested.

Opioid innervation of the caudal ventrolateral medulla is not critical for the expression of the aortic depressor nerve response in the rabbit.

PubMed

Drolet, G; Morilak, D A; Chalmers, J

1991-01-01

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

PubMed Central

de Oliveira, Lais Moraes; Rodrigues, Aline Gabriela; da Silva, Elaine Fernanda; Cerqueira, Letícia Bonancio; Castro, Carlos Henrique; Pedrino, Gustavo Rodrigues; de Carvalho, Maria Helena Catelli; Pontarolo, Roberto; Costa, Elson Alves; Campos, Francinete Ramos; Filgueira, Fernando Paranaiba; Ghedini, Paulo César

2012-01-01

Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway. PMID:22927883

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

PubMed

Wong, Dennis T L; Bertaso, Angela G; Liew, Gary Y H; Thomson, Viji S; Cunnington, Michael S; Richardson, James D; Gooley, Robert; Lockwood, Siobhan; Meredith, Ian T; Worthley, Matthew I; Worthley, Stephen G

2013-04-01

Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Hydrogen sulfide protects endothelial nitric oxide function under conditions of acute oxidative stress in vitro.

PubMed

Al-Magableh, Mohammad R; Kemp-Harper, Barbara K; Ng, Hooi H; Miller, Alyson A; Hart, Joanne L

2014-01-01

The aim of this study was to examine the ability of H2S, released from NaHS to protect vascular endothelial function under conditions of acute oxidative stress by scavenging superoxide anions (O2(-)) and suppressing vascular superoxide anion production. O2(-) was generated in Krebs' solution by reacting hypoxanthine with xanthine oxidase (Hx-XO) or with the O2(-) generator pyrogallol to model acute oxidative stress in vitro. O2(-) generation was measured by lucigenin-enhanced chemiluminescence. Functional responses in mouse aortic rings were assessed using a small vessel myograph. NaHS scavenged O2(-) in a concentration-dependent manner. Isolated aortic rings exposed to either Hx-XO or pyrogallol displayed significantly attenuated maximum vasorelaxation responses to the endothelium-dependent vasodilator acetylcholine, and significantly reduced NO bioavailability, which was completely reversed if vessels were pre-incubated with NaHS (100 μM). NADPH-stimulated aortic O2(-) production was significantly attenuated by the NADPH oxidase inhibitor diphenyl iodonium. Prior treatment of vessels with NaHS (100 nM-100 μM; 30 min) inhibited NADPH-stimulated aortic O2(-) production in a concentration-dependent manner. This effect persisted when NaHS was washed out prior to measuring NADPH-stimulated O2(-) production. These data show for the first time that NaHS directly scavenges O2(-) and suppresses vascular NADPH oxidase-derived O2(-) production in vitro. Furthermore, these properties protect endothelial function and NO bioavailability in an in vitro model of acute oxidative stress. These results suggest that H2S can elicit vasoprotection by both scavenging O2(-) and by reducing vascular NADPH oxidase-derived O2(-) production.

Vasorelaxant and cardiovascular properties of the essential oil of Pogostemon elsholtzioides.

PubMed

Shiva Kumar, Arumugasamy; Jeyaprakash, Karnan; Chellappan, David Raj; Murugan, Ramar

2017-03-06

Pogostemon elsholtzioides Benth. (Lamiaceae) is an aromatic shrub, endemic to eastern Himalaya region. The leaves are used for treating goiter and high blood pressure (BP) by indigenous people in Arunachal Pradesh, India. Young leaves are used as vegetable and leaf decoction is also used for cough, cold and headache by some indigenous communities in Northeast India. This species is used for treating hypertension and the genus Pogostemon is rich in essential oil. Therefore, the present study was aimed at investigation of the chemical constituents, vasorelaxant and cardiovascular effects of the essential oil of P. elsholtzioides. P. elsholtzioides was collected from Pasighat, Arunachal Pradesh, India and essential oil was extracted from shade dried leaves. Essential oil was analyzed by GC-FID and GC-MS and the volatile constituents were identified. Vasorelaxant and cardiovascular properties of the essential oil were studied against phenylephrine induced contraction in isolated endothelium intact aortic preparations and by measuring systolic and diastolic BP, mean arterial pressure (MAP) and heart rate (HR) after carotid artery cannulation in Wistar rats. The essential oil was rich in sesquiterpenes and curzerene, benzophenone, α-cadinol and germacrone were major constituents. The essential oil exhibited significant vasodilation effect in phenylephrine induced contracted aortic rings. Vasorelaxant effect of the essential oil was also observed both in the presence and absence of Nitro-L-arginine methyl ester against phenylephrine-contracted aortic rings. It also induced reduction of systolic and diastolic BP, MAP and HR. Essential oil of P. elsholtzioides exhibited significant vasorelaxant effect against endothelium intact aortic preparation mediated through nitric oxide dependent pathway and also reduced BP. However, further study is needed to screen the role of calcium ions in both intracellular and extracellular pathway. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

PubMed

Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

2008-07-04

In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, p<0.05). In addition, the average percentage of aortic lesions in the entire aorta area in the rabbits intranasally vaccinated with nanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, p<0.01) and was similar to those intramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

The effect of social environment on markers of vascular oxidative stress and inflammation in the Watanabe heritable hyperlipidemic rabbit.

PubMed

Nation, Daniel A; Gonzales, Julie A; Mendez, Armando J; Zaias, Julia; Szeto, Angela; Brooks, Larry G; Paredes, Jamespaul; D'Angola, Alyssa; Schneiderman, Neil; McCabe, Philip M

2008-04-01

Previous research demonstrated that social environment can influence progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. This study examined the effect of social environment on markers of oxidative stress and inflammation to clarify the physiological pathways potentially responsible for the influence of social environment on disease. WHHL rabbits were assigned to 1 of 3 social groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily; and an individually-caged group. The stable group engaged in more affiliative social behavior than the unstable group. The unstable group showed more agonistic behavior compared with the stable group and higher C-reactive protein levels than the individually caged group. The individually caged group was behaviorally sedentary, had higher 24-hour urinary catecholamine levels than the other groups, and exhibited higher NAD(P)H-oxidase activity in the aortic arch relative to the stable group. The results suggest that social environment creates distinct behavioral contexts that can affect markers of inflammation and oxidative stress early in the development of atherosclerosis. Specifically, physical inactivity associated with individual caging affects indices of oxidative stress and inflammation. These pathophysiological markers may help to explain behaviorally related differences in the extent of atherosclerosis observed in prior studies.

Changes of blood biochemistry in the rabbit animal model in atherosclerosis research; a time- or stress-effect

PubMed Central

2011-01-01

Background Rabbits are widely used in biomedical research and especially as animal models in atherosclerosis studies. Blood biochemistry is used to monitor progression of disease, before final evaluation including pathology of arteries and organs. The aim of the present study was to assess the consistency of the biochemical profile of New Zealand White rabbits on standard diet from 3 to 6 months of age, during which they are often used experimentally. Methods and results Eight conventional male 3-month-old New Zealand White rabbits were used. Blood samples were taken at baseline, 1, 2 and 3 months later. Plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol concentrations, and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and malondialdehyde were measured. Statistically significant time-related changes were observed in glucose, total cholesterol and triacylglycerol, which were not correlated with aortic lesions at 6 months of age. Similarly, hepatic enzyme activity had significant time-related changes, without a corresponding liver pathology. Conclusions Age progression and stress due to single housing may be the underlying reasons for these biochemistry changes. These early changes, indicative of metabolic alterations, should be taken into account even in short-term lipid/atherosclerosis studies, where age and standard diet are not expected to have an effect on the control group of a study. PMID:21838924

Intimal cushions and endothelial nuclear elongation around mouse aortic branches and their spatial correspondence with patterns of lipid deposition

PubMed Central

Bond, Andrew R.; Ni, Chih-Wen; Jo, Hanjoong

2010-01-01

Spatial variation in hemodynamic stresses acting on the arterial wall may explain the nonuniform distribution of atherosclerosis. In thoracic aortas of LDL receptor/apolipoprotein E double knockout mice, lesions develop preferentially around the entire circumference of intercostal branch ostia, regardless of age, with the highest prevalence occurring upstream. Additional chevron-shaped lesions occur further upstream of the ostia. This pattern differs from the age-related ones occurring in people and rabbits. In the present study, patterns of near-wall blood flow around intercostal ostia in wild-type mice were estimated from the morphology of endothelial nuclei, which were shown in vitro to elongate in response to elevated shear stress and to align with the flow, and wall structure was assessed from confocal and scanning electron microscopy. A triangular intimal cushion surrounded the upstream part of most ostia. Nuclear length-to-width ratios were lowest over this cushion and highest at the sides of branches, regardless of age. Nuclear orientations were consistent with flow diverging around the branch. The pattern of nuclear morphology differed from the age-related ones observed in rabbits. The intimal cushion and the distribution of shear stress inferred from these observations can partly account for the pattern of lesions observed in knockout mice. Nuclear elongation in nonbranch regions was approximately constant across animals of different size, demonstrating the existence of a mechanism by which endothelial cells compensate for the dependence of mean aortic wall shear stress on body mass. PMID:19933414

Ultrafine particulate matter exposure in vitro impairs vasorelaxant response in superoxide dismutase 2 deficient and aged murine aortic rings

EPA Science Inventory

Epidemiological studies positively associate exposure to inhaled ultrafine particulate matter (UFPM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure....

[Effects of black and red rice on the formation of aortic plaques and blood lipids in rabbits].

PubMed

Chen, Q; Ling, W; Ma, J; Mei, J

2000-05-30

In order to observe the antiatherosclerotic effects of black and red rice and to find out their mechanism, 24 New Zealand male white rabbits (average body weight 1.91 kg) were divided randomly into three groups (white rice, black rice and red rice groups). The rabbits were fed a cholesterol-enriched diet (cholesterol 5 g/kg, lard 35 g/kg) containing 300 g/kg white, black and red rice powder respectively. The rabbits were sacrificed 10 weeks later. The aorta was dissected and stained in 0.5% oilred-isopropanol solution. The plaque area and total area of aorta were measured by an automatic image analyzer. Serum lipids were determined by an automatic analyzer. The results showed that the plaque area (% of total surface) in the black and red rice groups was significantly lower than that in the white rice group (P < 0.05). Serum TG, TC, LDL-C, ApoB and ApoAI/ApoB were not significantly different among the three groups (P > 0.05). However, the concentrations of HDL-C and ApoAI were significantly higher in the black and red rice groups than those in the white groups (P < 0.05). No significant difference was found between the black and red rice groups. It is concluded that black and red rice might be effective in reducing atherosclerotic plaques on the aorta of rabbits fed a cholesterol-enriched diet. The effectiveness of black and red rice against atherosclerosis might be related to the high level of serum HDL-C and ApoAI.

Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: implications for transcatheter aortic valve therapies.

PubMed

Philip, Femi; Faza, Nadine Nadar; Schoenhagen, Paul; Desai, Milind Y; Tuzcu, E Murat; Svensson, Lars G; Kapadia, Samir R

2015-08-01

Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV). We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents. Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents. © 2015 Wiley Periodicals, Inc.

Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and /sup 45/Ca-fluxes in the rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, P.J.; Tetzloff, G.; Ahn, H.S.

1988-07-01

Vinpocetine is a highly specific inhibitor of calmodulin-dependent phosphodiesterase (CaM-PDE) with an IC50 of 19 microM and produces a significant accumulation of cyclic GMP but not cyclic AMP in rabbit aorta. In isolated rabbit aortic strips, vinpocetine (0.01 and 0.1 mM) inhibited the contraction and /sup 45/Ca uptake due to both phenylephrine (1 microM) and KCl (40 mM), whereas 8-Br-cyclic GMP (0.1-1mM) selectively impaired phenylephrine-induced responses. Furthermore, the KCl-stimulated /sup 45/Ca efflux in normal Ca2+ buffer, which reflects elevated cytosolic Ca2+, was greatly diminished by vinpocetine but not by 8-Br-cyclic GMP. However, phenylephrine-induced /sup 45/Ca efflux and contraction in Ca2+-freemore » buffer, which reflect Ca2+ release from intracellular sites, were similarly inhibited by both vinpocetine and 8-Br-cyclic GMP. The results suggest that vinpocetine may effect vasodilatation through blockade of the slow channel and selective inhibition of CaM-PDE in the vascular smooth muscle.« less

Effect of choline magnesium trisalicylate on prostacyclin production by isolated vascular tissue of the rat.

PubMed

Levy, J V

1983-01-15

Choline Magnesium Trisalicylate (Trilisate), in therapeutic concentrations of 5, 10, 15 and 30 mg/100 ml, did not significantly affect production of prostacyclin-like (PGI2) substance by rat aortic tissue in vitro. The ED50 for inhibition of aorta PGI2-like substance production by Trilisate was 1,200 mg/100 ml. This is approximately 40 times the maximum therapeutic blood concentration achieved in humans. Choline or Magnesium salicylate produced slight but insignificant inhibition of PGI2-like substance production by rat aortic tissue in vitro. The ED50 for ibuprofen (Motrin) for inhibition of PGI2-like production of rat aortic rings was 0.65-0.92 mg/100 ml. Injection of Choline Magnesium Trisalicylate into rats (124, 250, 500 mg/kg I.P.) did not affect the normal production of PGI2-like substance of aortic tissue obtained one hour after in vivo treatment. These results suggest this anti-inflammatory salicylate does not adversely affect PGI2-like production by blood vessels, in concentrations associated with therapeutic effects in man.

The induction by X-rays of chromosome aberrations in male guinea-pigs, golden hamsters and rabbits. II. Properties of translocations induced in post-meiotic stages.

PubMed

Cox, B D; Lyon, M F

1975-07-01

Translocations induced by X-rays in post-meiotic germ cells of male guinea-pigs, golden hamsters and rabbits were studied cytologically in the F1 sons of the irradiated males. The percentage of spermatocytes displaying multivalent configurations varied with the translocation, but the average percentage appeared to depend on the species: fewer quadrivalents were observed in hamster than in guinea-pig heterozygotes and most were recorded for rabbit heterozygotes. Chain quadrivalents were more abundant than ring quadrivalents at meiosis for the guinea-pig and hamster, in contrast to the mouse. Too few translocation heterozygotes were examined to determine which meiotic configuration was the more prevalent in the rabbit. In all three species, as in the mouse, translocations were found which caused male sterility, due to partial or complete failure of spermatogenesis, although most translocations caused semi-sterility. For these semi-sterile males both the frequency and time of embryonic death in the progeny appeared to be the same as in the mouse. It is concluded that similar types of chromosome aberrations are induced by X-rays in post-meiotic germ cells of male guinea-pigs, rabbits, golden hamsters and mice.

A geometric approach to aortic root surgical anatomy.

PubMed

Contino, Monica; Mangini, Andrea; Lemma, Massimo Giovanni; Romagnoni, Claudia; Zerbi, Pietro; Gelpi, Guido; Antona, Carlo

2016-01-01

The aim of this study was the analysis of the geometrical relationships between the different structures constituting the aortic root, with particular attention to interleaflet triangles, haemodynamic ventriculo-arterial junction and functional aortic annulus in normal subjects. Sixteen formol-fixed human hearts with normal aortic roots were studied. The aortic root was isolated, sectioned at the midpoint of the non-coronary sinus, spread apart and photographed by a high-resolution digital camera. After calibration and picture resizing, the software AutoCAD 2004 was used to identify and measure all the elements of the interleaflets triangles and of the aortic root that were objects of our analysis. Multiple comparisons were performed with one-way analysis of variance for continuous data and with Kruskal-Wallis analysis for non-continuous data. Linear regression and Pearson's product correlation were used to correlate root element dimensions when appropriate. Student's t-test was used to compare means for unpaired data. Heron's formula was applied to estimate the functional aortic annular diameters. The non coronary-left coronary interleaflets triangles were larger, followed by inter-coronary and right-non-coronary ones. The apical angle is <60° and its standard deviation can be considered an asymmetry index. The sinu-tubular junction was shown to be 10% larger than the virtual basal ring (VBR). The mathematical relationship between the haemodynamic ventriculo-arterial junction and the VBR calculated by linear regression and expressed in terms of the diameter was: haemodynamic ventriculo-arterial junction = 2.29 VBR (diameter) + 47. Conservative aortic surgery is based on a better understanding of aortic root anatomy and physiology. The relationships among its elements are of paramount importance during aortic valve repair/sparing procedures and they can be useful also in echocardiographic analysis and in computed tomography reconstruction. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels

NASA Technical Reports Server (NTRS)

Berkowitz, Dan E.; White, Ron; Li, Dechun; Minhas, Khalid M.; Cernetich, Amy; Kim, Soonyul; Burke, Sean; Shoukas, Artin A.; Nyhan, Daniel; Champion, Hunter C.;

Correlation of leukocyte adhesiveness, adhesion molecule expression and leukocyte-induced contraction following balloon angioplasty

PubMed Central

Kennedy, Simon; McPhaden, Allan R; Wadsworth, Roger M; Wainwright, Cherry L

2000-01-01

The aim of this study was to examine the changes in leukocyte adhesion and leukocyte-induced contraction in balloon-injured rabbit subclavian artery and to correlate these changes with vessel morphology and expression of adhesion molecules on the injured arteries.Rabbits were anaesthetized and their left subclavian arteries were injured by balloon inflation and withdrawal followed by sacrifice at 2, 24, 48 h or 8 days after injury. The left and right subclavian arteries were removed and leukocytes were isolated from autologous rabbit blood. Leukocyte-induced contraction was measured in 5-HT precontracted artery rings and leukocyte adhesion was measured using 51Cr-labelled leukocytes. Immunocytochemistry using paraffin-embedded tissue was employed to detect changes in the expression of adhesion molecules on injured arteries.Autologous leukocytes caused a contraction of rabbit subclavian artery rings, which was prevented by L-NAME (10−3 M). Balloon-induced injury abolished the contractile response to leukocytes, which correlated with loss of carbachol-induced relaxationBalloon injury markedly enhanced the adhesiveness of the subclavian artery for leukocytes, most notably at 24 and 48 h after injury (1.7 and 1.8 fold respectively). Increased leukocyte adhesion at these two time points correlated with an upregulation of E-selectin, P-selectin and VCAM-1 expression on the remaining endothelium of the injured artery.Vessel morphology revealed that balloon inflation had induced an infiltration of inflammatory cells into the vessel wall, the greatest increase being seen at 24 h after injury.It is concluded that an increase in the expression of E-selectin, P-selectin and VCAM-1 following balloon-induced injury leads to enhanced leukocyte adhesion and migration into the injured vessel. PMID:10781003

Pharmacologic study of calcium influx pathways in rabbit aortic smooth muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lukeman, D.S.

1987-01-01

Functional characteristics and pharmacologic domains of receptor-operated and potential-sensitive calcium (Ca/sup 2 +/) channels (ROCs and PSCs, respectively) were derived via measurements of /sup 45/Ca/sup 2 +/ influx (M/sup Ca/) during activation by the neurotransmitters norepinephrine (NE), histamine (HS), and serotonin (5-HT) and by elevated extracellular potassium (K/sup +/) in the individual or combined presence of organic Ca/sup 2 +/ channel antagonists (CAts), calmodulin antagonists (Calm-ants), lanthanum (La/sup 3 +/), and agents that increase intracellular levels of cyclic AMP.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload.

PubMed

Apitz, Christian; Honjo, Osami; Humpl, Tilman; Li, Jing; Assad, Renato S; Cho, Mi Y; Hong, James; Friedberg, Mark K; Redington, Andrew N

2012-12-01

Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor β genes. Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Decreased expression of γ-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein.

PubMed

Doyon, Marielle; Mathieu, Patrick; Moreau, Pierre

2013-02-01

Arterial stiffness is accelerated in type 1 diabetic patients. Medial artery calcification (MAC) contributes to the development of arterial stiffness. Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by γ-carboxylase to activate matrix γ-carboxyglutamic acid (Gla) protein (MGP), an inhibitor of vascular calcification. This study aimed to evaluate the hypothesis that diabetes reduces the γ-carboxylation of MGP in the aortic wall, leading to increased vascular calcification, and the role of γ-carboxylase and VKOR in this γ-carboxylation deficit. Type 1 diabetes was induced in male Wistar rats with a single ip injection of streptozotocin. Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase in aortic pulse wave velocity. Aortic and femoral calcification were increased by 26 and 56%, respectively. γ-Carboxylated MGP (cMGP, active) was reduced by 36% and the aortic expression of γ-carboxylase was reduced by 58%. Expression of γ-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r = -0.57). VKOR aortic expression and activity were not modified by diabetes. Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex vivo experiments with aortic rings, vitamin K supplementation prevented the glucose-induced decrease in γ-carboxylase expression. Our results suggest that reduced cMGP, through an impaired expression of γ-carboxylase, is involved in the early development of MAC in diabetes, and therefore, in the acceleration of arterial stiffness. A defect in vitamin K uptake by target cells could also be involved.

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

PubMed

Devlin, A M; Brosnan, M J; Graham, D; Morton, J J; McPhaden, A R; McIntyre, M; Hamilton, C A; Reid, J L; Dominiczak, A F

1998-01-01

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed.

PubMed

Runnie, I; Salleh, M N; Mohamed, S; Head, R J; Abeywardena, M Y

2004-06-01

In this study, the vasodilatory actions of nine edible tropical plant extracts were investigated. Ipomoea batatas (sweet potato leaf), Piper betle (betel leaf), Anacardium occidentale (cashew leaf), Gynandropsis gynandra (maman leaf), Carica papaya (papaya leaf), and Mentha arvensis (mint leaf) extracts exhibited more than 50% relaxing effect on aortic ring preparations, while Piper betle and Cymbopogon citratus (lemongrass stalk) showed comparable vasorelaxation on isolated perfused mesenteric artery preparation. The vascular effect on the aortic ring preparations were mainly endothelium-dependent, and mediated by nitric oxide (NO) as supported by the inhibition of action in the presence of N(omega)-nitro-L-arginine (NOLA), an nitric oxide synthase (NOS) inhibitor, or by the removal of endothelium. In contrast, vasodilatory actions in resistance vessels (perfused mesenteric vascular beds) appear to involve several biochemical mediators, including NO, prostanoids, and endothelium-dependent hyperpolarizing factors (EDHFs). Total phenolic contents and antioxidant capacities varied among different extracts and found to be independent of vascular relaxation effects. This study demonstrates that many edible plants common in Asian diets to possess potential health benefits, affording protection at the vascular endothelium level.

Vasorelaxant and antihypertensive effects of methanolic fraction of the essential oil of Alpinia zerumbet.

PubMed

da Cunha, Gilmara Holanda; de Moraes, Manoel Odorico; Fechine, Francisco Vagnaldo; Frota Bezerra, Fernando Antônio; Silveira, Edilberto Rocha; Canuto, Kirley Marques; de Moraes, Maria Elisabete Amaral

2013-01-01

Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, several pathways involved in the mechanism of vasorelaxation are still unclear. This study was designed to verify the antihypertensive effect of the methanolic fraction of the essential oil of A. zerumbet (MFEOAz) and to characterize its mechanism of action. The thoracic aortic rings from the Wistar rats were perfused in the organ chambers filled with Kreb's solution, where the tension of each ring was measured. The antihypertensive effect of MFEOAz was assessed in rats submitted to chronic hypertension by inhibition of nitric oxide synthesis by indirect measurement of blood pressure with indirect tail cuff method. MFEOAz relaxed phenylephrine and KCl-induced contraction of either endothelium-intact or endothelium-denuded rat aortic rings in a concentration-dependent manner. Pre-incubation with MFEOAz (100 and 300 μg/mL) in Ca(2+)-free Krebs solution attenuated phenylephrine- or caffeine-induced contraction. Pre-incubation with L-NAME, ODQ, wortmannin, atropine, indomethacin, catalase, SOD, TEA, 4-aminopyridine, glibenclamide, apamin, charybdotoxin, or iberiotoxin did not affect MFEOAz-induced relaxation. The intragastric administration of MFEOAz induced an antihypertensive effect. MFEOAz it seems inhibited the calcium influx via voltage-operated calcium channels and receptor-operated calcium channels, as well as inhibition of calcium mobilization from intracellular stores. Copyright © 2013 Elsevier Inc. All rights reserved.

Closed transventricular dilation of discrete subvalvular aortic stenosis in dogs.

PubMed

Linn, K; Orton, E C

1992-01-01

Discrete subvalvular aortic stenosis with peak systolic pressure gradients of more than 60 mm Hg was treated by closed transventricular dilation in six young dogs. Peak systolic pressure gradients were measured by direct catheterization before surgery, immediately after dilation, and 3 months after surgery. Maximum instantaneous pressure gradients were measured by continuous wave Doppler echocardiography before surgery and 6 weeks to 9 months after surgery. All dogs survived the procedure, and two dogs were clinically normal after 9 and 14 months. Two dogs died at week 6 and month 7. One dog was receiving medication for pulmonary edema 15 months after surgery. One dog underwent open resection of the subvalvular ring at month 3, and was clinically normal 6 months after the second procedure. Complications included intraoperative ventricular fibrillation in one dog, and mild postoperative aortic insufficiency in one dog. Closed transventricular dilation resulted in an immediate 83% decrease in the peak systolic pressure gradient from a preoperative mean of 97 +/- 22 mm Hg to a mean of 14 +/- 15 mm Hg. However, systolic pressure gradients measured by direct catheterization at month 3 (77 +/- 26 mm Hg), and by Doppler echocardiography at week 6 to month 9 (85 +/- 32 mm Hg) were not significantly different from preoperative values, which suggested recurrence of the aortic stenosis. Closed transventricular dilation should not be considered a definitive treatment for discrete subvalvular aortic stenosis in dogs, but may be useful in young dogs with critical aortic stenosis as a bridge to more definitive surgery.

Sulforaphane, a Natural Isothiocyanate Compound, Improves Cardiac Function and Remodeling by Inhibiting Oxidative Stress and Inflammation in a Rabbit Model of Chronic Heart Failure.

PubMed

Ma, Tongliang; Zhu, Decai; Chen, Duoxue; Zhang, Qiaoyun; Dong, Huifang; Wu, Wenwu; Lu, Huihe; Wu, Guangfu

2018-03-12

BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to detect levels of inflammatory cytokines, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS In the CHF group, compared with the sham operation group, there was an increase in the heart weight to body weight ratio (HW/BW), the left ventricular weight to body weight ratio (LVW/BW), the left ventricular end diastolic diameter (LVEDD), the left ventricular end systolic diameter (LVESD), plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels, the cardiac collagen volume fraction (CVF), apoptotic index, expression levels of collagen I, collagen III, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in the myocardial tissue, and a decrease in the left ventricular shortening fraction (LVFS) and left ventricular ejection fraction (LVEF), and cardiac superoxide dismutase (SOD) activity. These changes were corrected in the SFN-treated group. CONCLUSIONS In a rabbit model of CHF, treatment with SFN improved cardiac function and remodeling by inhibiting oxidative stress and inflammation.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

PubMed Central

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Chronic psychological stress induces vascular inflammation in rabbits.

PubMed

Lu, Xiao Ting; Liu, Yun Fang; Zhao, Li; Li, Wen Jing; Yang, Rui Xue; Yan, Fang Fang; Zhao, Yu Xia; Jiang, Fan

2013-01-01

Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-α, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-α neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-α and p38/JNK pathways, which may contribute to the development of atherosclerosis.

Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

PubMed

Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

2015-09-01

The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p < 0.05), 62 were elevated and five decreased in ascending aortas from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring, which confirmed the iTRAQ results. Many of the observed protein changes are consistent with known molecular perturbations in the ascending aorta that occur in response to hypercholesterolemia, e.g. elevation of tissue levels of apolipoproteins, extracellular matrix adhesion proteins, glycolytic enzymes, heat shock proteins and proteins involved in immune defense. We also made a number of novel observations, including a 15-fold elevation of glycoprotein (trans-membrane) nmb-like (Gpnmb) in response to HCD. Gpnmb has previously been linked to angiogenesis but not to atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Purification and partial characterization of a novel lectin from Dioclea lasiocarpa Mart seeds with vasodilator effects.

PubMed

do Nascimento, Antônia Sâmia F; Gondim, Ana Cláudia S; Cajazeiras, João B; Correia, Jorge Luis A; Pires, Alana de F; do Nascimento, Kyria S; da Silva, André Luis C; Nagano, Celso S; Assreuy, Ana Maria S; Cavada, Benildo S

2012-12-01

A lectin from seeds of Dioclea lasiocarpa (DLL) was purified in a single step by affinity chromatography in a Sephadex G-50 column. DLL haemagglutinated rabbit erythrocytes showing stability even after 1 h of exposure to a different pH values (optimal between pH 6.0 and 8.0) but was inhibited after incubation with D-mannose and D-glucose. The pure protein possessed a molecular weight of 25 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and 25,410Da by mass spectrometry. The results analyzed by the software SELCON 3 indicate that β-sheet secondary structures are predominant in DLL (approximately 40.2% antiparallel β-sheet, 4.6% parallel β-sheet, 7.2% α-helices, 17.3% turns, and 28.7% unordered structures). Mechanical activity of isolated aorta from rat measured by cumulative concentration curves of DLL, performed at the contraction plateau induced by phenylephrine in either endothelium-intact or denuded aorta. DLL (IC(50)  = 34.12 ± 3.46 µg/ml) relaxed precontracted endothelized aortic rings by 34.61 ± 9.06%, 55.19 ± 11.9%, and 81.33 ± 14.35%, respectively, at 10 µg/ml (initial concentration), 30 µg/ml, and 100 µg/ml (maximum effect). All effects occurred via interaction with lectin domains and participation of nitric oxide. Copyright © 2012 John Wiley & Sons, Ltd.

Gerbode defect and multivalvular dysfunction: Complex complications in adult congenital heart disease.

PubMed

Ruivo, Catarina; Guardado, Joana; Montenegro Sá, Fernando; Saraiva, Fátima; Antunes, Alexandre; Correia, Joana; Morais, João

2017-07-01

We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description. © 2017, Wiley Periodicals, Inc.

Echocardiographic features of the normofunctional Labcor-Santiago pericardial bioprosthesis.

PubMed

Gonzalez-Juanatey, J R; Garcia-Bengoechea, J B; Vega, M; Rubio, J; Sierra, J; Duran, D; Amaro, A; Gil, M

1994-09-01

Echocardiography was performed in 94 patients with a total of 99 normally functioning Labcor-Santiago bioprostheses, 62 in the aortic and 37 in the mitral position. The following variables were measured: peak and mean transvalvular velocities, peak and mean instantaneous pressure gradients as calculated from the modified Bernoulli equation, pressure half-time, cardiac index, stroke volume and effective orifice area (using continuity and Hatle equations). Regurgitation patterns were sought by transthoracic echocardiography (all valves) and, for selected mitral bioprostheses, by transesophageal echocardiography. Calculated mean aortic pressure gradient ranged from six to 10 mmHg and calculated effective aortic orifice area increased with ring diameter, with means of 1.27 cm2 for the 19 mm valve and 2.58 cm2 for the 27 mm valve. For mitral bioprostheses, mean pressure gradient ranged from 3.0 to 4.5 mmHg and calculated effective orifice area from 2.27 to 2.73 cm2. Only central regurgitation was observed. The Labcor-Santiago pericardial bioprostheses created little resistance to forward flow. In the small aortic root their hemodynamic performance was as good or better than that of other currently available devices. It is hoped that this new design will contribute increased in vivo mechanical durability.

Successful surgical treatment of intramural aortoatrial fistula, severe aortic regurgitation, mitral prolapse, and tricuspid insufficiency in a patient with Ehlers-Danlos syndrome type IV.

PubMed

Jiang, Shengli; Gao, Changqing; Ren, Chonglei; Zhang, Tao

2012-06-01

Patients with Ehlers-Danlos syndrome (EDS) type IV, an inherited connective tissue disorder, are predisposed to vascular and digestive ruptures, and arterial ruptures account for the majority of deaths. A 31-year-old man with EDS presented with an intramural aortoatrial fistula, severe aortic regurgitation, mitral valve prolapse, and severe tricuspid valve insufficiency combined with a severely dilated left ventricle. Determining the best surgical option for the patient was not easy, especially regarding the course of action for the aortic root with a tear in the sinus of Valsalva. The fistula tract was closed at the aorta with suture and with a patch in the right atrium, the mitral valve was repaired with edge-to-edge suture and then annuloplasty with a Cosgrove ring, the aortic valve was replaced with a mechanical prosthesis, and a modified De Vega technique was used for the tricuspid valvuloplasty. The postoperative course was uncomplicated, and the patient was discharged 2 weeks later. The considerations made to arrive at the chosen surgical course of action in this complex case are reviewed.

[Simultaneous interventions on the ascending portion, arch of the aorta and cardiac valves in patients with Marfan's syndrome].

PubMed

Belov, Iu V; Stepanenko, A B; Gens, A P; Charchian, E R; Savichev, D D

2007-01-01

Simultaneous surgical interventions on the aorta and valvular system of the heart were performed in four patients presenting with aortic dissections and aneurysms conditioned by Marfan's syndrome. The following reconstructive operations were carried out: 1) prosthetic repair of the aortic valve and the ascending portion of the aorta by means of a valve-containing conduit with replantation of the openings of the coronary arteries into the side of the prosthesis according to the Benthall - De Bono technique, annuloplasty of the tricuspid valve according to the De Vega technique, valvuloplasty of the mitral valve by the Alferi technique; 2) grafting of the aortic valve and the ascending portion of the aorta by means of a valve-containing conduit with replantation of the openings of the coronary arteries according to the Kabrol's technique, plasty of the tricuspid valve by the De Vega technique; 3) prosthetic repair of the aortic arch with distal wedge-like excision of the membrane of the dissection and directing the blood flow along the both channels, plasty of the mitral valve, plasty of the aortic valve and the ascending portion of the aorta with a valve-containing conduit, accompanied by replantation of the openings of the coronary arteries into the side of the graft according to the Benthall - De Bono technique; (4) plasty of the mitral valve with a disk graft through the fibrous ring of the aortic valve, prosthetic repair of the aortic valve and the ascending portion of the aorta with a valve-containing conduit, accompanied by replantation of the openings of the coronary arteries into the side according to the Benthall-De Bono technique.

Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci.

PubMed

Anguita-Alonso, Paloma; Rouse, Mark S; Piper, Kerryl E; Steckelberg, James M; Patel, Robin

2006-04-01

The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 microg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 microg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 microg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2x10(6) IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax)/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment (P<0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and Cmax/MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

Increased vascular sensitivity and connexin43 expression after sympathetic denervation.

PubMed

Slovut, David P; Mehta, Shyamal H; Dorrance, Anne M; Brosius, Frank C; Watts, Stephanie W; Webb, R Clinton

2004-05-01

Following denervation, arteries demonstrate a heightened sensitivity to alpha-adrenergic agonists and increased oscillatory contractions that may partly result from increased gap junction expression. Hence, we wanted to study the effect of sympathetic denervation on connexin43 (Cx43) expression and agonist-induced contractility in the vascular smooth muscle (VSM). Effects of denervation with reserpine (3 mg/kg/day, i.p.) or topical 5% phenol-glycerol on VSM contractions and expression of the gap junction Cx43 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting for Cx43 protein were examined. Wistar-Kyoto (WKY) rat tail arteries were exposed to norepinephrine (NE) (10(-9)-10(-5) M). Reactivity was also examined in the carotid arteries and thoracic aortas from Cx43 heterozygote deficient (KO) mice. The concentration for NE-induced contraction was lower in reserpine- and phenol-treated vessels than controls (p<0.05). NE-induced oscillatory activity (OA) was seen in 5/5 reserpine- and 5/8 phenol-treated vessels vs. 0/12 controls (p<0.05). Spontaneous OA was observed more frequently in carotid and aortic rings from WT than Cx43 KO rings. Cumulative OA in response to alpha-adrenergic stimulation was significantly greater in WT carotid (429+/-101 vs. 128+/-7 mN s, p<0.05) and aortic rings (337+/-85 vs. 134+/-11 mN s, p<0.05) than in Cx43 KO rings. Following denervation, RT-PCR showed significantly increased levels of Cx43 mRNA (p<0.05). Western blot analysis revealed near doubling of Cx43 protein (p<0.05). We conclude that sympathetic denervation results in increased expression of Cx43, which in turn, contributes to increased spontaneous and agonist-induced OA in VSM.

Nitric oxide production contributes to Bacillus anthracis edema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat

PubMed Central

Li, Yan; Cui, Xizhong; Xu, Wanying; Ohanjanian, Lernik; Sampath-Kumar, Hanish; Suffredini, Dante; Moayeri, Mahtab; Leppla, Stephen; Fitz, Yvonne

2016-01-01

We showed previously that Bacillus anthracis edema toxin (ET), comprised of protective antigen (PA) and edema factor (EF), inhibits phenylephrine (PE)-induced contraction in rat aortic rings and these effects are diminished in endothelial-denuded rings. Therefore, employing rat aortic ring and in vivo models, we tested the hypothesis that nitric oxide (NO) contributes to ET's arterial effects. Compared with rings challenged with PA alone, ET (PA + EF) reduced PE-stimulated maximal contractile force (MCF) and increased the PE concentration producing 50% MCF (EC50) (P < 0.0001). Compared with placebo, l-nitro-arginine methyl-ester (l-NAME), an NO synthase (NOS) inhibitor, reduced ET's effects on MCF and EC50 in patterns that approached or were significant (P = 0.06 and 0.03, respectively). In animals challenged with 24-h ET infusions, l-NAME (0.5 or 1.0 mg·kg−1·h−1) coadministration increased survival to 17 of 28 animals (60.7%) compared with 4 of 27 (14.8%) given placebo (P = 0.01). Animals receiving l-NAME but no ET all survived. Compared with PBS challenge, ET increased NO levels at 24 h and l-NAME decreased these increases (P < 0.0001). ET infusion decreased mean arterial blood pressure (MAP) in placebo and l-NAME-treated animals (P < 0.0001) but l-NAME reduced decreases in MAP with ET from 9 to 24 h (P = 0.03 for the time interaction). S-methyl-l-thiocitrulline, a selective neuronal NOS inhibitor, had effects in rings and, at a high dose in vivo models, comparable to l-NAME, whereas N′-[3-(aminomethyl)benzyl]-acetimidamide, a selective inducible NOS inhibitor, did not. NO production contributes to ET's arterial relaxant, hypotensive, and lethal effects in the rat. PMID:27448553

Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model.

PubMed

Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Masumoto, Asuka; Nakashima, Yuri; Ito, Teppei; Mima, Toru; Negi, Shigeo; Kimura-Suda, Hiromi; Shigematsu, Takashi

2017-06-01

Previous clinical and experimental studies have indicated that magnesium may prevent vascular calcification (VC), but mechanistic characterization has not been reported. This study investigated the influence of increasing magnesium concentrations on VC in a rat aortic tissue culture model. Aortic segments from male Sprague-Dawley rats were incubated in serum-supplemented high-phosphate medium for 10 days. The magnesium concentration in this medium was increased to demonstrate its role in preventing VC, which was assessed by imaging and spectroscopy. The mineral composition of the calcification was analyzed using Fourier transform infrared (FTIR) spectroscopic imaging, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) mapping. Magnesium supplementation of high-phosphate medium dose-dependently suppressed VC (quantified as aortic calcium content), and almost ablated it at 2.4 mm magnesium. The FTIR images and SEM-EDX maps indicated that the distribution of phosphate (as hydroxyapatite), phosphorus and Mg corresponded with calcium content in the aortic ring and VC. The inhibitory effect of magnesium supplementation on VC was partially reduced by 2-aminoethoxy-diphenylborate, an inhibitor of TRPM7. Furthermore, phosphate transporter-1 (Pit-1) protein expression was increased in tissues cultured in HP medium and was gradually-and dose dependently-decreased by magnesium. We conclude that a mechanism involving TRPM7 and Pit-1 underpins the magnesium-mediated reversal of high-phosphate-associated VC.

Chronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2.

PubMed

Qu, Chen; Leung, Susan W S; Vanhoutte, Paul M; Man, Ricky Y K

2010-08-01

Acute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg) or vehicle (distilled water; 1 ml/kg). Chronic treatment with L-NAME increased arterial blood pressure. Isometric tension was measured in aortic rings with or without endothelium. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore 5-(methylamino)-2-[(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187) were reduced in preparations from L-NAME-treated rats. The reduction in relaxation to A23187 was partially reversed by L-arginine (1 mM). In quiescent aortic rings, A23187 caused contractions in the presence of L-NAME and intact endothelium. The A23187-induced contractions were greater in rings from the L-NAME-treated rats than in those from the control group. These contractions were abolished by the cyclooxygenase (COX)-2 inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS-398) and the thromboxane-prostanoid (TP) receptor antagonist 3-((6R)-6-{[(4-chlorophenyl)sulfonyl]amido}-2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)propanoate (S18886), but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560). Chronic L-NAME treatment reduced the level of nitric oxide in the plasma but increased COX activity in the aortic rings. Western blotting and immunohistochemical staining showed that endothelial NOS expression was reduced in the aortae of the chronic L-NAME-treated group. COX-1 expression was augmented slightly, whereas COX-2 expression was up-regulated markedly. The TP receptor expression was comparable with control. These experiments demonstrate that chronic NOS inhibition increases endothelium-dependent contractions of the rat aorta by inducing COX-2 expression and augmenting the production of EDCF.

The influence of methionine-5-enkephalin on calcium uptake by the bovine aortic media.

PubMed

Kokkas, B; Kotoula, M; Kouyoumtzis, A; Kouvelas, D; Papadopoulos, K; Paradelis, A G

1990-04-01

The influence of methionine-5-enkephalin (M-5-E), an endogenous opioid receptor agonist, on calcium uptake by bovine aortic media was investigated in vitro. 45Ca was used and radioactivity was counted in a beta scintillation counter. M-5-E increases Ca2+ uptake by the preparation. This action is inhibited by naloxone and that is proof that an opioid receptor is stimulated. A comparative study showed that phenylephrine, an alpha-adrenoceptor agonist, exhibits the same action as M-5-E, whereas morphine's action is negligible. Phenylephrine contracts the deendotheliazed ring of the bovine aorta, whereas M-5-E fails to do so. It is concluded that an opioid receptor was identified at the bovine aortic smooth muscle. This receptor is stimulated by M-5-E resulting in an increase of the extracellular Ca2+ entrance. Although no relationship was observed between the receptor and the contraction mechanism, a possible role of M-5-E in the maintenance of the vascular tone cannot be excluded.

Magnolol attenuates VCAM-1 expression in vitro in TNF-α-treated human aortic endothelial cells and in vivo in the aorta of cholesterol-fed rabbits

PubMed Central

Chen, Yung-Hsiang; Lin, Shing-Jong; Chen, Jaw-Wen; Ku, Hung-Hai; Chen, Yuh-Lien

2002-01-01

In a previous study, we showed that magnolol, a potent antioxidant derived from a Chinese herb, attenuates monocyte chemotactic protein-1 (MCP-1) expression and intimal hyperplasia in the balloon-injured aorta of cholesterol-fed rabbits. Expression of cell adhesion molecules by the arterial endothelium and the attachment of leukocytes to the endothelium may play a major role in atherosclerosis. In the present study, the effects of magnolol on the expression of endothelial-leukocyte adhesion molecules and the activation of nuclear factor kappa B (NF-κB) in tumour necrosis factor-α (TNF-α)-treated human aortic endothelial cells (HAECs) were investigated.Pretreatment of HAECs with magnolol (5 μM) significantly suppressed the TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) (64.8±1.9%), but had no effect on the expression of intercellular cell adhesion molecule-1 and endothelial cell selectin.Magnolol (5 and 10 μM) significantly reduced the binding of the human monocytic cell line, U937, to TNF-α-stimulated HAECs (58.4 and 56.4% inhibition, respectively). Gel shift assays using the 32P-labelled NF-κB consensus sequence as probe showed that magnolol pretreatment reduced the density of the shifted bands seen after TNF-α-induced activation. Immunoblot analysis and immunofluorescence staining of nuclear extracts demonstrated a 58% reduction in the amount of NF-κB p65 in the nuclei in magnolol-treated HAECs. Magnolol also attenuated intracellular H2O2 generation in both control and TNF-α treated HAECs.Furthermore, in vivo, magnolol attenuates the intimal thickening and TNF-α and VCAM-1 protein expression seen in the thoracic aortas of cholesterol-fed rabbits.Taken together, these data demonstrate that magnolol inhibits TNF-α-induced nuclear translocation of NF-κB p65 and thereby suppresses expression of VCAM-1, resulting in reduced adhesion of leukocytes. These results suggest that magnolol has anti-inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory responses in vivo. PMID:11786478

Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia.

PubMed

Lozos, Vasileios A; Toumpoulis, Ioannis K; Agrogiannis, Georgios; Giamarellos-Bourboulis, Evangelos J; Chamogeorgakis, Themistocles P; Rizos, Ioannis K; Patsouris, Efstratios S; Anagnostopoulos, Constantine E; Rokkas, Chris K

2013-01-01

Potassium adenosine triphosphate (KATP) channel openers have been involved in the enhancement of ischemic tolerance in various tissues. The purpose of the present study is to evaluate the effects of aprikalim, a specific KATP channel opener, on spinal cord ischemic injury. Fifty-four rabbits were randomly assigned to three groups: group 1 (n = 18, sham operation), group 2 (n = 18, 30 min of normothermic aortic cross-clamping) and group 3 (n = 18, aprikalim 100 μg/kg was administered 15 min before 30 min of normothermic aortic cross-clamping). Neurologic evaluation was performed according to the modified Tarlov scale. Six animals from each group were sacrificed at 24, 48 and 168 h postoperatively. The lumbar spinal cords were harvested and examined histologically. The motor neurons were counted and the histologic lesions were scored (0-3, 3: normal). Group 3 (aprikalim group) had better Tarlov scores compared to group 2 at all-time points (P < 0.025). The histologic changes were proportional to the Tarlov scores and group 3 had better functional outcome as compared to group 2 at 168 h (number of neurons: 21.2 ± 4.9 vs. 8.0 ± 2.7, P < 0.001 and histologic score: 1.67 ± 1.03 vs. 0.50 ± 0.55, P = 0.03). Although aprikalim exhibited improved effect on clinical and histologic neurologic outcome when compared to normothermic spinal cord ischemia, animals in group 3 had worse Tarlov score, reduced number of motor neurons and worse histologic score when compared to group 1 (sham operation) at 168 h (P = 0.003, P = 0.001 and P = 0.019 respectively). Aprikalim reduces the severity of spinal cord ischemic injury in a rabbit model of spinal cord ischemia. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

PubMed

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

In vitro and ex vivo angiogenic effects of roxarsone on rat endothelial cells.

PubMed

Zhu, Jiaqiao; Cui, Weibo; Liu, Xue; Ying, Jun; Hu, Chengyun; Zhang, Yumei

2013-11-25

Roxarsone, a feed additive, is being used worldwide to promote animal growth. However, the potential effect of roxarsone on angiogenesis has not been extensively characterized. We examined the ability of roxarsone to promote angiogenesis of rat endothelial cells in vitro and from rat aorta rings ex vivo. Endothelial cells from rats were exposed to 0.01-10.00μM roxarsone, 5ng/mL vascular endothelial growth factor (VEGF) as a positive control or phosphate buffer saline (PBS) as a negative control. Cell proliferation was measured by MTT assay, and the content of VEGF in supernatants was measured by enzyme-linked immunosorbent assay and Western blotting. A Matrigel-induced tube formation assay was used to evaluate the effects of roxarsone on endothelial cells. Additionally, the total number and length of microvessels sprouted from rat aortic rings were measured for ex vivo investigation of angiogenesis. Results showed that the cell viability and total number and length of capillary-like tube formations after roxarsone treatment was significantly higher than that of negative (P<0.05), with a maximum effect at 1.00μM exposure. Furthermore, the number of microvessels sprouted from aortic rings treated for 4h with 0.1-10.0μM roxarsone was significantly higher than that of PBS treatment, with a peak value of 1.0μM. These results further demonstrate the potential of roxarsone to promote angiogenesis in vitro and ex vivo. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-angiogenic and cytotoxicity studies of some medicinal plants.

PubMed

Ng, Kwok-Wen; Salhimi, Salizawati Muhamad; Majid, Amin Malik; Chan, Kit-Lam

2010-06-01

Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation. Georg Thieme Verlag KG Stuttgart-New York.

Ergothioneine prevents endothelial dysfunction induced by mercury chloride.

PubMed

Gökçe, Göksel; Arun, Mehmet Zuhuri; Ertuna, Elif

2018-06-01

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low-dose mercury chloride (HgCl 2 ). Agonist-induced contractions and relaxations were evaluated in isolated aortic rings from 3-month-old male Wistar rats treated by intra-muscular injection to caudal hind leg muscle with HgCl 2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin- and luminol-enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low-dose HgCl 2 administration impaired acetylcholine (ACh)-induced relaxation and potentiated phenylephrine- and serotonin-induced contractions in rat aortas. In addition, HgCl 2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh-induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low-dose HgCl 2 administration. EGT may serve as a therapeutic tool to reduce mercury-associated cardiovascular complications via improving the antioxidant status.

[Correction of the endothelial function damaged by gamma-irradiation with free and liposomal quercetin].

PubMed

Kyslova, O V; Sapatyĭ, A L; Kupnovyts'ka, I H; Moĭbenko, O O

2007-01-01

It has been investigation the action of solubil quercetin (corvitin) and quercetin filled liposomes (lipoflavon) on endothelium--dependent r-irradiated isolated rats aortic rings relaxations to acetylcholine. It has been showed, that corvitin addition directly to the buffer solution (0.1 mg/ml) increase endothelium--dependent vascular responses to acetylcholine on 35%, lipoflavon addition--on 25%.

Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.

PubMed

Azarmi, Yadollah; Babaei, Hossein; Alizadeh, Fatemeh; Gharebageri, Afsaneh; Fouladi, Daniel F; Nikkhah, Elhameh

2014-02-01

Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 μM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.

A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture.

PubMed

de Vega, Susana; Suzuki, Nobuharu; Nonaka, Risa; Sasaki, Takako; Forcinito, Patricia; Arikawa-Hirasawa, Eri; Yamada, Yoshihiko

2014-03-01

We have previously demonstrated that fibulin-7 (Fbln7) is expressed in teeth by pre-odontoblast and odontoblast cells, localized in the basement membrane and dentin matrices, and is an adhesion molecule for dental mesenchyme cells and odontoblasts. Fbln7 is also expressed in blood vessels by endothelial cells. In this report, we show that a recombinant C-terminal Fbln7 fragment (Fbln7-C) bound to Human Umbilical Vein Endothelial Cells (HUVECs) but did not promote cell spreading and actin stress fiber formation. Fbln7-C binding to HUVECs induced integrin clustering at cell adhesion sites with other focal adhesion molecules, and sustained activation of FAK, p130Cas, and Rac1. In addition, RhoA activation was inhibited, thereby preventing HUVEC spreading. As endothelial cell spreading is an important step for angiogenesis, we examined the effect of Fbln7-C on angiogenesis using in vitro assays for endothelial cell tube formation and vessel sprouting from aortic rings. We found that Fbln7-C inhibited the HUVEC tube formation and the vessel sprouting in aortic ring assays. Our findings suggest potential anti-angiogenic activity of the Fbln7 C-terminal region. Published by Elsevier Inc.

Chemical Composition, Toxicity and Vasodilatation Effect of the Flowers Extract of Jasminum sambac (L.) Ait. "G. Duke of Tuscany".

PubMed

Kunhachan, Phanukit; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat; Khayungarnnawee, Amonrat; Leelamanit, Wichet

2012-01-01

Phytochemical analysis of the ethanolic Jasmine flower extract of Jasminum sambac (L.) Ait. "G. Duke of Tuscany" revealed the mixtures of coumarins, cardiac glycosides, essential oils, flavonoids, phenolics, saponins, and steroids. However, alkaloids, anthraquinones, and tannins were not detected. By intravenous injection at a single dose of 0.5 mL/mouse (15 mg) of the flower extract, no systemic biological toxicity demonstrated in ICR mice was observed. In Wistar rats, the LD(50) of the extract was higher than 5,000 mg/kg BW by oral administration. Vasodilatation effect of the 95% ethanolic extract on isolated aortic rats was also investigated. Compared with the control group, the Jasmine flowers extract in 0.05% DMSO clearly reduced tonus of isolated endothelium thoracic aortic rings preconstricted with phenylephrine (10(-6) M), as a dose-dependent manner. Nevertheless, this pharmacological effect disappeared after the preincubation of the rings with atropine (10(-6) M) or with N(ω)-nitro-L-arginine (10(-4) M). These are possibly due to the actions of the active components on the vessel muscarinic receptors or by causing the release of nitric oxide.

Changes of imidazoline receptors in spontaneously hypertensive rats

PubMed Central

Mar, Guang-Yuan; Chou, Ming-Ting; Chung, Hsien-Hui; Chiu, Nien-Hua; Chen, Mei-Fen; Cheng, Juei-Tang

2013-01-01

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1-receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2-receptor, which is expressed more highly in SHRs. PMID:23176371

Posterior capsule opacification in rabbit eyes implanted with 1-piece and 3-piece hydrophobic acrylic intraocular lenses.

PubMed

Werner, Liliana; Mamalis, Nick; Izak, Andrea M; Pandey, Suresh K; Davis, Brandon L; Nilson, Chistian D; Weight, Christopher; Apple, David J

2005-04-01

To evaluate the outcome of posterior capsule opacification (PCO) after implantation in rabbit eyes of currently available 3-piece and 1-piece hydrophobic acrylic intraocular lenses (IOLs) with square optic edges. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. The 3-piece designs evaluated were the AR40e (Advanced Medical Optics Inc.) and the MA60AC (Alcon, Inc.); the 1-piece designs were the SA60AT and the SA30AT (Alcon, Inc.). Nine lenses of each type were implanted in a randomized manner by the same surgeon in 18 Dutch Belted pigmented rabbits. After a follow-up of 3 weeks, the rabbits were killed and analyses of the enucleated eyes were performed from the posterior or Miyake-Apple view. The intensity of central PCO, peripheral PCO, and Soemmering's ring formation was scored from 0 to 4. The area of Soemmering's ring formation was also scored from 0 to 4 based on the number of quadrants involved. Other parameters analyzed were capsulorhexis coverage of the IOL anterior surface, IOL centration, fixation, and presence of striae. Results from the posterior view were complemented by histopathologic evaluation of the eyes. No statistically significant difference was found between the 4 groups of IOLs in the parameters analyzed from the posterior view. When cell ingrowth occurred with the 1-piece designs, causing peripheral and central PCO formation, it was more likely to start at the optic-haptic junctions, as observed during the clinical follow-up with slitlamp examination and confirmed by gross and histopathologic analyses of the enucleated eyes. The square, truncated optic edge is the most important IOL design feature for PCO prevention. The optic-haptic junctions of the 1-piece designs appear to be sites where the barrier effect of the truncated optic edge is less effective.

Effect of H-7 on secondary cataract after phacoemulsification in the live rabbit eye.

PubMed

Tian, Baohe; Heatley, Gregg A; Filla, Mark S; Kaufman, Paul L

2010-12-01

This study is aimed to determine if the serine-threonine kinase inhibitor H-7 inhibits secondary cataract after phacoemulsification in the live rabbit eye. Eighteen rabbits underwent extracapsular lens extraction by phacoemulsification in 1 eye. The eye was treated with intravitreal H-7 (300 or 1,200 μM; n = 6 or 5) or balanced salt solution (BSS) (n = 7) immediately after the surgery and twice weekly for 10 weeks. Each eye received slit lamp biomicroscopy once a week, during which posterior capsule opacification (PCO) was evaluated. The eye was then enucleated and the lens capsule was prepared, fixed, and imaged. PCO was evaluated again on the isolated lens capsule under a phase microscope. Soemmering's ring area (SRA) and the entire lens capsule area were measured from capsule images on a computer and the percentage of SRA (PSRA) in the entire capsule area was calculated. Wet weight of the capsule (WW) was determined on a balance. No significant difference in PCO was observed in any comparison. No significant differences in SRA, PSRA, and WW were observed between the 300 μM H-7-treated eye and the BSS-treated eye. However, SRA, PSRA, and WW in the 1,200 μM H-7-treated eye were significantly smaller than those in the BSS-treated eye [28.3 ± 16.2 vs. 61.4 ± 8.86 mm(2) (P = 0.001), 33% ± 20% vs. 65% ± 15% (P = 0.01), and 65.6 ± 27.9 vs. 127.0 ±37.3 mg (P = 0.01)]. Intravitreal H-7 (1,200 μM) significantly inhibits Soemmering's ring formation in the live rabbit eye, suggesting that agents that inhibit the actomyosin system in cells may prevent secondary cataract after phacoemulsification.

Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

PubMed

Prabhakar, N R; Runold, M; Yamamoto, Y; Lagercrantz, H; Cherniack, N S; von Euler, C

1987-09-01

Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Obtaining the biomechanical behavior of ascending aortic aneurysm via the use of novel speckle tracking echocardiography.

PubMed

Alreshidan, Mohammed; Shahmansouri, Nastaran; Chung, Jennifer; Lash, Vynka; Emmott, Alexander; Leask, Richard L; Lachapelle, Kevin

2017-04-01

Ex vivo measurement of ascending aortic biomechanical properties may help understand the risk for rupture or dissection of dilated ascending aortas. A validated in vivo method that can predict aortic biomechanics does not exist. Speckle tracking transesophageal echocardiography (TEE) has been used to measure ventricular stiffness; we sought to determine whether speckle TEE could be adapted to estimate aortic stiffness in vivo and compare these findings with those obtained by ex vivo tissue measurements. A total of 17 patients undergoing ascending aortic resection were recruited to with a mean aortic diameter was 56.16 ± 15 mm. Intraoperative speckle TEE tracking analysis was used to calculate aortic stiffness index using the following equation: β2=ln(SBP/DBP)/AoS, where β2 is the stiffness index; SBP is systolic blood pressure; DBP is diastolic blood pressure; and AoS is the circumferential strain. Ex vivo stiffness was obtained by mechanical tissue testing according to previously described methods. The aortic ring at the pulmonary trunk was divided into 4 equal quadrants. The in vivo stiffness index for the inner curvature, anterior wall, outer curvature, and posterior wall were 0.0544 ± 0.0490, 0.0295 ± 0.0199, 0.0411 ± 0.0328, and 0.0502 ± 0.0320, respectively. The mean ex vivo 25% apparent stiffness for inner curvature, anterior wall, outer curvature, and posterior wall were 0.0616 ± 0.0758 MPa, 0.0352 ± 0.00992 MPa, 0.0405 ± 0.0199 MPa, and 0.0327 ± 0.0106 MPa, respectively. The patient-matched ex vivo 25% apparent stiffness and in vivo stiffness index were not significantly different (P = .8617, 2-way analysis of variance with repeated measures). The use of speckle TEE appears to be a promising technique to estimate ex vivo mechanical properties of the ascending aortic tissue. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

Effects of protopine on intracellular calcium and the PKC activity of rat aorta smooth muscle.

PubMed

Li, Bin; Wu, Qin; Shi, Jing-Shan; Sun, An-Sheng; Huang, Xie-Nan

2005-04-25

We have previously shown that the vasodilator effect of protopine (Pro) on rabbit aorta is related to the elevations of cAMP and cGMP. In the present study, the vasodilator mechanisms of Pro were further explored by recording the isotonic contraction of the rat aortic strips, detecting directly the intracellular free Ca(2+) concentration ([Ca(2+)](i)) with Fura-2/AM loaded vascular smooth muscle cells (VSMCs) of rat aorta, and determining the activity of protein kinase C (PKC) in rat aortic tissue with radioactive isotope gamma-32P -ATP-catalyzing assay. By recording the aortic strips contraction induced by noradrenaline (NA) and high potassium (K(+)), Pro shifted nonparallelly the concentration-response curves of NA and high K(+) to right, in which the maximal response was depressed in the presence of Pro (30 and 100 micromol/L), and the values of pD'(2) were 3.70-/+0.25 and 3.97-/+0.15 for NA and high K(+), respectively. In the Fura-2/AM loaded VSMCs, Pro (50 and 100 micromol/L) could not produce any significant change on the resting [Ca(2+)](i), but significantly decreased the [Ca(2+)](i) elevated by NA and high K(+). Pro (30 and 100 micromol/L) had no significant effect on the activity of the cytosolic and membrane PKC in the aortic strips inpretreated by NA. However, in the aortic strips pretreated by NA, the activity of membrane PKC was significantly increased and the activity of cytosolic PKC tended to be decreased by Pro, while the activity of total PKC did not change. These results suggest that Pro seems to promote the translocation of PKC from the cytosol to the membrane in the presence of NA, its vasodilator effect may be the comprehensive result of its decreasing effect on the [Ca(2+)](i) and the increasing effect on cAMP and cGMP, as well as its influence on the PKC.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

PubMed Central

2013-01-01

Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/−) mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE−/− and the wild-type (WT) mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress. PMID:23289368

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms.

PubMed

Musabayane, Cephas T; Kamadyaapa, Dave R; Gondwe, Mavuto; Moodley, Kogi; Ojewole, John A O

2008-01-01

The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control, 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl saltsensitive (DSS) genetically hypertensive rats, which progressively develop hypertension with age, treated with HCE (80 mg/kg) every third consecutive day for seven weeks. Isolated atrial muscle strips, portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p < 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentrationdependent negative inotropic and chronotropic effects on rat isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced, but not completely abolished by adding endothelial- derived factor (EDRF) inhibitor, L-NAME, suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited, in part, directly by decreasing myocardial contractile performance and total peripheral vascular resistance due to its negative inotropic and chronotropic effects on rat isolated atrial muscle strips; and vasorelaxant effects on isolated vascular smooth muscles. The observed cardiovascular effects of HCE partly support the basis for its use in the management of high blood pressure in folkloric medicine.

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms

PubMed Central

Musabayane, Cephas T; Kamadyaapa, Dave R; Gondwe, Mavuto; Moodley, Kogi; Ojewole, John AO

2008-01-01

Summary Summary The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control, 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl salt-sensitive (DSS) genetically hypertensive rats, which progressively develop hypertension with age, treated with HCE (80 mg/kg) every third consecutive day for seven weeks. Isolated atrial muscle strips, portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p < 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentration-dependent negative inotropic and chronotropic effects on rat isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced, but not completely abolished by adding endothelial-derived factor (EDRF) inhibitor, L-NAME, suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited, in part, directly by decreasing myocardial contractile performance and total peripheral vascular resistance due to its negative inotropic and chronotropic effects on rat isolated atrial muscle strips; and vasorelaxant effects on isolated vascular smooth muscles. The observed cardiovascular effects of HCE partly support the basis for its use in the management of high blood pressure in folkloric medicine. PMID:18997985

Altitude negates the benefits of aerobic training on the vascular adaptations in rats.

PubMed

Reboul, Cyril; Tanguy, Stephane; Dauzat, Michel; Obert, Philippe

2005-06-01

This study questioned the effect of living and training at moderate altitude on aortic vasoreactivity. Considering that chronic hypoxia exposure and endurance training are able to generate opposite effects on the systemic vascular reactivity, it was hypothesized that endurance training benefits on the vascular function could be limited by chronic hypoxia. Sea-level native rats were randomly assigned to N (living in normoxia), NT (living and training 5 d.wk for 5 wk in normoxia), CH (living in hypoxia, 2800 m), and CHT (living and training 5 d.wk for 5 wk in hypoxia, 2800 m) groups. Concentration response curves to epinephrine, norepinephrine, endothelin-1, acetylcholine, and sodium nitro-prusside were assessed on aortic isolated rings. Left ventricular resting and maximal (during Tyrode's infusion) stroke volumes were evaluated by Doppler-echocardiography and used as indexes of chronic aortic volume overload. The main finding was that favorable aortic vasoreactivity adaptations consecutive to sea-level training were not observed when training was conducted at altitude. An improvement in the endothelium-dependent vasorelaxation (maximal relaxation, R(max), N = 60.4 +/- 10.0 vs NT = 91.7 +/- 3.2%; P < 0.05) and a reduced sensitivity to ET-1 were observed in NT rats. Such an enhancement in endothelium-dependent vasorelaxation was not found in CHT rats (R(max): 48.4 +/- 7.8%). Moreover, a higher sensitivity to ET-1 was reported in this group. Altitude-induced limitation in aortic blood flow and shear stress could play a major role in the explanation of these specific altitude-training adaptations. If extrapolated to the peripheral vascular bed, our results have practical significance for aerobic performance as aortic vasoreactivity adaptations after altitude training could contribute to limit blood delivery to exercising muscles.

Effect of cholesterol lowering on stiffness of aortic and femoral arterial walls in rabbits on a high fat diet.

PubMed

Xue, Li; Xu, Wan-Hai; Xu, Jin-Zhi; Zhang, Tong; Bi, Hong-Yuan; Shen, Bao-Zhong

2009-06-20

Researches in arterial elasticity have increased over the past few years. We investigated the effects of simvastatin on vascular stiffness in fat fed rabbits by ultrasonography. Thirty rabbits were assigned randomly to 3 groups: normal control group (A), the cholesterol group (B), simvastatin group (C: high fat diet for 4 weeks and high fat diet + simvastatin for further 4 weeks). Stiffness coefficient, pressure strain elastic modulus and velocity of pulse waves in abdominal aorta and femoral artery were measured by ultrasonographic echo tracking at the end of the 4th and the 8th weeks. At the end of the 4th week, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly increased in group B compared with those in group A. Similarly, at the end of the 8th week, the same parameters of abdominal aorta were significantly increased in group B compared with those in group A. In contrast, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly decreased in group C compared with those in group B, however, there was no significant difference in parameters of abdominal aorta between groups B and C. Short term administration of simvastatin can improve the elasticity of femoral artery but not abdominal aorta.

A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure.

PubMed

Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei; Sun, Li-Zhong

2015-04-01

The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients' mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation in which a working model is required.

Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet

PubMed Central

Amran, Adel A.; Zakaria, Zaiton; Othman, Faizah; Das, Srijit; Al-Mekhlafi, Hesham M.; Raj, Santhana; Nordin, Nor-Anita MM

2012-01-01

Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion. PMID:27366140

ATP sensitive K+ channel subunits (Kir6.1, Kir6.2) are the candidate mediators regulating ameliorating effects of pulsed magnetic field on aortic contractility in diabetic rats.

PubMed

Ocal, Isil; Yilmaz, Mehmet B; Kocaturk-Sel, Sabriye; Tufan, Turan; Erkoc, Mehmet A; Comertpay, Gamze; Oksuz, Hale; Barc, Esma D

2018-05-01

Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (K ATP ) in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled-diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF for a period of 6 weeks according to the PMF application protocol (1 h/day; intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF exposure, body weight and blood glucose levels were measured. Then, thoracic aorta tissue was extracted for relaxation-contraction and Kir6.1 and Kir6.2 expression experiments. Blood plasma glucose levels, body weight, and aortic ring contraction percentage decreased in controlled-diabetic rats but increased in non-controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non-controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2 mRNA expressions were repressed both in controlled diabetic and non-controlled diabetic rats by PMF. Our findings suggest that the positive therapeutic effects of PMF may act through (K ATP ) subunits and may frequently occur in insulin-free conditions. Bioelectromagnetics. 39:299-311, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological cardiovascular alterations induced by glutathione depletion in rats.

PubMed

Rossoni, Giuseppe; Manfredi, Barbara; Tazzari, Valerio; Sparatore, Anna; Trivulzio, Silvio; Del Soldato, Piero; Berti, Ferruccio

2010-12-01

We investigated the effects of the hydrogen sulfide (H₂S)-releasing derivatives of aspirin (ACS14) and salicylic acid (ACS21) in a rat model of metabolic syndrome induced by glutathione (GSH) depletion, causing hypertension and other pathological cardiovascular alterations. GSH depletion was induced in normal rats by the GSH-synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L day for seven days in the drinking water). Systolic blood pressure and heart rate were measured daily by the tail-cuff method, and plasma thromboxane B₂, 6-keto-prostaglandin F(2α), 8-isoprostane, GSH, insulin and glucose were determined at the end of the seven-day BSO schedule. In addition, ischemia/reperfusion-induced myocardial dysfunction and endothelial dysfunction were assayed on isolated heart and aortic rings, respectively. Unlike aspirin and salicylic acid, ACS14 and ACS21 reduced BSO-induced hypertension, also lowering plasma levels of thromboxane B₂, 8-isoprostane and insulin, while GSH remained in the control range. Neither ACS14 nor ACS21 caused gastric lesions. Both restored the endothelial dysfunction observed in aortic rings from BSO-treated rats, and in ischemia/reperfusion experiments they lowered left ventricular end-diastolic pressure, consequently improving the developed pressure and the maximum rise and fall of left ventricular pressure. Together with this improvement of heart mechanics there were reductions in the activity of creatine kinase and lactate dehydrogenase in the cardiac perfusate. This implies that H₂S released by both ACS14 and ACS21 was involved in protecting the heart from ischemia/reperfusion, and significantly limited vascular endothelial dysfunction in aortic tissue and the related hypertension. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of the dB-c-AMP and forskolin on /sup 45/Ca influx, net Ca uptake and tension on rabbit aortic smooth muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-03-01

The effect of dibutiryl-adenosine-3',5'-cyclic-monophosphate (dB-c-AMP) and forskolin on aortic tension and /sup 45/Ca influx were measured. dB-c-AMP reduced both the rate of force development and the maximal tension achieved in solutions containing various K/sup +/ concentrations. Stimulated /sup 45/Ca influx was also reduced however to a lesser extent than was the tension. Forskolin showed more marked effects of a similar nature. Thus, both these agents which increase intracellular c-AMP caused a rightward shift in the curve expressing force(ordinate) as a function of Ca influx (abscissa). Consequently, they found that dB-c-AMP stimulated more net Ca to be taken up by themore » sarcoplasmic reticulum(SR) at the same influx rate. The conclusion that c-AMP produced these effects by stimulating Ca uptake into the superficial SR was supported by the finding that dB-c-AMP increased the amount of Ca taken up into a caffeine releasable fraction.« less

Yoda1 analogue (Dooku1) which antagonizes Yoda1‐evoked activation of Piezo1 and aortic relaxation

PubMed Central

Evans, Elizabeth L; Cuthbertson, Kevin; Endesh, Naima; Rode, Baptiste; Blythe, Nicola M; Hyman, Adam J; Hall, Sally J; Gaunt, Hannah J; Ludlow, Melanie J

2018-01-01

Background and Purpose The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small‐molecule agonist, but the pharmacology of these channels is otherwise limited. Experimental Approach Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta. Key Results Modification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2 μM Yoda1‐induced Ca2+‐entry with IC50s of 1.3 μM (HEK 293 cells) and 1.5 μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP‐evoked Ca2+ elevation or store‐operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose‐dependent relaxation of aortic rings, which was mediated by an endothelium‐ and NO‐dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1. Conclusion and Implications Chemical antagonism of Yoda1‐evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains. PMID:29498036

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists.

PubMed

Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

2012-07-15

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite.

PubMed

Damacena-Angelis, Célio; Oliveira-Paula, Gustavo H; Pinheiro, Lucas C; Crevelin, Eduardo J; Portella, Rafael L; Moraes, Luiz Alberto B; Tanus-Santos, Jose E

2017-08-01

Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR) mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion) to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite ( 15 N-nitrite) by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Nitrate exerted no effect on aortic accumulation of 15 N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in the Michaelis constant. Together, our results show that nitrate inhibits XOR-mediated NO production from nitrite, and this mechanism may explain how nitrate attenuates the vascular and blood pressure responses to nitrite. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorim, Jonaina, E-mail: nanafiorim@hotmail.com; Ribeiro Júnior, Rogério Faustino, E-mail: faustino43@oi.com.br; Azevedo, Bruna Fernades, E-mail: brunafernandes.azevedo@gmail.com

Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K{sup +} channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K{sup +} channels and Na{sup +}/K{sup +}-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100 g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilatormore » response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O{sub 2}{sup −} production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K{sup +}-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K{sup +}-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K{sup +} channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress. -- Highlights: ► Increased free radicals production ► Increased Na{sup +}/K{sup +} ATPase activity ► Promotes activation of the K{sup +} channels and reduced vascular reactivity ► These effects preserve endothelial function against oxidative stress. ► Low concentrations constitute environmental cardiovascular risk factor.« less

Chemical Composition, Toxicity and Vasodilatation Effect of the Flowers Extract of Jasminum sambac (L.) Ait. “G. Duke of Tuscany”

PubMed Central

Kunhachan, Phanukit; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat; Khayungarnnawee, Amonrat; Leelamanit, Wichet

2012-01-01

Phytochemical analysis of the ethanolic Jasmine flower extract of Jasminum sambac (L.) Ait. “G. Duke of Tuscany” revealed the mixtures of coumarins, cardiac glycosides, essential oils, flavonoids, phenolics, saponins, and steroids. However, alkaloids, anthraquinones, and tannins were not detected. By intravenous injection at a single dose of 0.5 mL/mouse (15 mg) of the flower extract, no systemic biological toxicity demonstrated in ICR mice was observed. In Wistar rats, the LD50 of the extract was higher than 5,000 mg/kg BW by oral administration. Vasodilatation effect of the 95% ethanolic extract on isolated aortic rats was also investigated. Compared with the control group, the Jasmine flowers extract in 0.05% DMSO clearly reduced tonus of isolated endothelium thoracic aortic rings preconstricted with phenylephrine (10−6 M), as a dose-dependent manner. Nevertheless, this pharmacological effect disappeared after the preincubation of the rings with atropine (10−6 M) or with Nω-nitro-L-arginine (10−4 M). These are possibly due to the actions of the active components on the vessel muscarinic receptors or by causing the release of nitric oxide. PMID:22536286

Vasodilatory effects and underlying mechanisms of the ethyl acetate extracts from Gastrodia elata.

PubMed

Dai, Rong; Wang, Ting; Si, Xiaoqin; Jia, Yuanyuan; Wang, Lili; Yuan, Yan; Lin, Qing; Yang, Cui

2017-05-01

The objective of this study was to assess the ethyl acetate extracts of Gastrodia elata Blume (GEB) on vascular tone and the mechanisms involved. GEB was extracted with 95% EtOH followed by a further extraction with ethyl acetate. The effects of GEB and its ingredients on the isometric tensions of the aortic rings from rats were measured. The ethyl acetate extract of GEB induced a vasodilatory effect on rat aorta, which was partially dependent on endothelium. Four chemical compounds isolated from GEB were identified as 3,4-dihydroxybenzaldehyde (DB), 4-hydroxybenzaldehyde (HB), 4-methoxybenzyl alcohol (MA), and 4,4'-dihydroxydiphenyl methane (DM), respectively. All of these compounds induced vasodilatations, which were dependent on the endothelium to different degrees. After pretreatment with N ω -nitro-l-arginine methyl ester, indomethacin, or methylene blue, the vasodilatations induced by DB, HB, and MA were significantly decreased. In addition, the contractions of the rat aortic rings due to Ca 2+ influx and intracellular Ca 2+ release were also inhibited by DM. Furthermore, the administration of DB significantly enhanced the productions of nitric oxide (NO) and the activities of the endothelial NO synthase in aorta and in endothelial cells. Thus, GEB may play an important role in the amelioration of hypertension by modulating vascular tones.

Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

PubMed

Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

2000-04-01

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. Copyright 2000 S. Karger AG, Basel.

Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway

PubMed Central

Elmasri, Harun; Ghelfi, Elisa; Yu, Chen-wei; Traphagen, Samantha; Cernadas, Manuela; Cao, Haiming; Shi, Guo-Ping; Plutzky, Jorge; Sahin, Mustafa; Hotamisligil, Gokhan; Cataltepe, Sule

2013-01-01

Fatty acid binding protein 4 (FABP4) plays an important role in regulation of glucose and lipid homeostasis as well as inflammation through its actions in adipocytes and macrophages. FABP4 is also expressed in a subset of endothelial cells, but its role in this cell type is not known. We found that FABP4-deficient human umbilical vein endothelial cells (HUVECs) demonstrate a markedly increased susceptibility to apoptosis as well as decreased migration and capillary network formation. Aortic rings from FABP4−/− mice demonstrated decreased angiogenic sprouting, which was recovered by reconstitution of FABP4. FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin. FABP4 modulated activation of several important signaling pathways in HUVECs, including downregulation of P38, eNOS, and stem cell factor (SCF)/c-kit signaling. Of these, the SCF/c-kit pathway was found to have a major role in attenuated angiogenic activity of FABP4-deficient ECs as provision of exogenous SCF resulted in a significant recovery in cell proliferation, survival, morphogenesis, and aortic ring sprouting. These data unravel a novel pro-angiogenic role for endothelial cell-FABP4 and suggest that it could be exploited as a potential target for diseases associated with pathological angiogenesis. PMID:22562362

Transesophageal echocardiographic strain imaging predicts aortic biomechanics: Beyond diameter.

PubMed

Emmott, Alexander; Alzahrani, Haitham; Alreishidan, Mohammed; Therrien, Judith; Leask, Richard L; Lachapelle, Kevin

2018-03-11

Clinical guidelines recommend resection of ascending aortic aneurysms at diameters 5.5 cm or greater to prevent rupture or dissection. However, approximately 40% of all ascending aortic dissections occur below this threshold. We propose new transesophageal echocardiography strain-imaging moduli coupled with blood pressure measurements to predict aortic dysfunction below the surgical threshold. A total of 21 patients undergoing aortic resection were recruited to participate in this study. Transesophageal echocardiography imaging of the aortic short-axis and invasive radial blood pressure traces were taken for 3 cardiac cycles. By using EchoPAC (GE Healthcare, Madison, Wis) and postprocessing in MATLAB (MathWorks, Natick, Mass), circumferential stretch profiles were generated and combined with the blood pressure traces. From these data, 2 in vivo stiffness moduli were calculated: the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. From the resected aortic ring, testing squares were isolated for ex vivo mechanical analysis and histopathology. Each square underwent equibiaxial tensile testing to generate stress-stretch profiles for each patient. Two ex vivo indices were calculated from these profiles (energy loss and incremental stiffness) for comparison with the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. The echo-derived stiffness moduli demonstrate positive significant covariance with ex vivo tensile biomechanical indices: energy loss (vs Cardiac Cycle Pressure Modulus: R 2  = 0.5873, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6401, P < .0001) and apparent stiffness (vs Cardiac Cycle Pressure Modulus: R 2  = 0.2079, P = .0378; vs Cardiac Cycle Stress Modulus: R 2  = 0.3575, P = .0042). Likewise, these transesophageal echocardiography-derived moduli are highly predictive of the histopathologic composition of collagen and elastin (collagen/elastin ratio vs Cardiac Cycle Pressure Modulus: R 2  = 0.6165, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6037, P < .0001). Transesophageal echocardiography-derived stiffness moduli correlate strongly with aortic wall biomechanics and histopathology, which demonstrates the added benefit of using simple echocardiography-derived biomechanics to stratify patient populations. Copyright © 2018. Published by Elsevier Inc.

Orthogonal Rings, Fiducial Markers, and Overlay Accuracy When Image Fusion is Used for EVAR Guidance.

PubMed

Koutouzi, G; Sandström, C; Roos, H; Henrikson, O; Leonhardt, H; Falkenberg, M

2016-11-01

Evaluation of orthogonal rings, fiducial markers, and overlay accuracy when image fusion is used for endovascular aortic repair (EVAR). This was a prospective single centre study. In 19 patients undergoing standard EVAR, 3D image fusion was used for intra-operative guidance. Renal arteries and targeted stent graft positions were marked with rings orthogonal to the respective centre lines from pre-operative computed tomography (CT). Radiopaque reference objects attached to the back of the patient were used as fiducial markers to detect patient movement intra-operatively. Automatic 3D-3D registration of the pre-operative CT with an intra-operative cone beam computed tomography (CBCT) as well as 3D-3D registration after manual alignment of nearby vertebrae were evaluated. Registration was defined as being sufficient for EVAR guidance if the deviation of the origin of the lower renal artery was less than 3 mm. For final overlay registration, the renal arteries were manually aligned using aortic calcification and vessel outlines. The accuracy of the overlay before stent graft deployment was evaluated using digital subtraction angiography (DSA) as direct comparison. Fiducial markers helped in detecting misalignment caused by patient movement during the procedure. Use of automatic intensity based registration alone was insufficient for EVAR guidance. Manual registration based on vertebrae L1-L2 was sufficient in 7/19 patients (37%). Using the final adjusted registration as overlay, the median alignment error of the lower renal artery marking at pre-deployment DSA was 2 mm (0-5) sideways and 2 mm (0-9) longitudinally, mostly in a caudal direction. 3D image fusion can facilitate intra-operative guidance during EVAR. Orthogonal rings and fiducial markers are useful for visualization and overlay correction. However, the accuracy of the overlaid 3D image is not always ideal and further technical development is needed. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

[Interspecies differences of noopept pharmacokinetics].

PubMed

Boĭko, S S; Korotkov, S A; Zherdev, V P; Gudasheva, T A; Ostrovskaia, R U; Voronina, T A

2004-01-01

Significant interspecific differences in the pharmacokinetics of noopept are manifested by a decrease in the drug elimination rate on the passage from rats to rabbits and humans. Very intensive metabolism of noopept was observed upon intravenous administration in rats. In these animals, presystemic elimination mechanisms lead to the formation of a specific metabolite representing a product of drug biotransformation hydroxylated at the phenyl ring. In rabbits, unchanged noopept circulates in the blood for a longer time upon both intravenous and peroral introduction, biotransformation proceeds at a much slower rate, and no metabolites analogous to that found in rats are detected. The noopept pharmacokinetics in humans differs from that in animals by still slower elimination and considerable individual variability. No drug metabolites are found in the human blood plasma, probably because of a relatively small dose and low concentration.

Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences.

PubMed Central

Belvisi, M. G.; Patacchini, R.; Barnes, P. J.; Maggi, C. A.

1994-01-01

1. Exogenous tachykinins modulate cholinergic neurotransmission in rabbit and guinea-pig airways. We have investigated the effect of selective tachykinin receptor agonists and antagonists on cholinergic neurotransmission evoked by electrical field stimulation (EFS) of bronchial rings in rabbit, guinea-pig and human airways in vitro to assess which type of tachykinin receptor is mediating this facilitatory effect. 2. Bronchial rings were set up for isometric tension recording. Contractile responses to EFS (60 V, 0.4 ms, 2 Hz for 10 s every min) and exogenous acetylcholine (ACh) were obtained and the effects of selective tachykinin agonists and antagonists were investigated. 3. In rabbit bronchi the endogenous tachykinins, substance P (SP) and neurokinin A (NKA) (10 nM) potentiated cholinergic responses to EFS (by 287.6 +/- 121%, P < 0.01 and 181.4 +/- 56.5%, P < 0.001 respectively). 4. The NK1 receptor selective agonist, [Sar9]SP sulphone (10 nM) evoked a maximal facilitatory action on cholinergic responses of 334.9 +/- 63% (P < 0.01) (pD2 = 8.5 +/- 0.06) an effect which was blocked by the selective NK1-receptor antagonist, CP 96,345 (100 nM) (P < 0.05) but not by the NK2 receptor antagonist, MEN 10,376 (100 nM). The NK2 receptor selective agonist, [beta Ala8]NKA(4-10) (10 nM), produced a maximum enhancement of 278 +/- 83.5% (P < 0.01) (pD2 = 8.7 +/- 0.1) an effect which was blocked by MEN 10,376 (100 nM) (P < 0.05) and not by CP 96,345. [MePhe7]NKB, an NK3 receptor selective agonist was without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7516799

Biotransformation of two β-secretase inhibitors including ring opening and contraction of a pyrimidine ring.

PubMed

Lindgren, Anders; Eklund, Göran; Turek, Dominika; Malmquist, Jonas; Swahn, Britt-Marie; Holenz, Jörg; von Berg, Stefan; Karlström, Sofia; Bueters, Tjerk

2013-05-01

Recently, the discovery of the aminoisoindoles as potent and selective inhibitors of β-secretase was reported, including the close structural analogs compound (S)-1-pyridin-4-yl-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine [(S)-25] and (S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine hemifumarate (AZD3839), the latter being recently progressed to the clinic. The biotransformation of (S)-25 was investigated in vitro and in vivo in rat, rabbit, and human and compared with AZD3839 to further understand the metabolic fate of these compounds. In vitro, CYP3A4 was the major responsible enzyme and metabolized both compounds to a large extent in the commonly shared pyridine and pyrimidine rings. The main proposed metabolic pathways in various in vitro systems were N-oxidation of the pyridine and/or pyrimidine ring and conversion to 4-pyrimidone and pyrimidine-2,4-dione. Both compounds were extensively metabolized, and more than 90% was excreted in feces after intravenous administration of radiolabeled compound to the rat. Here, the main pathways were N-oxidation of the pyridine and/or pyrimidine ring and a ring contraction of the pyrimidine ring into an imidazole ring. Ring-contracted metabolites accounted for 25% of the total metabolism in the rat for (S)-25, whereas the contribution was much smaller for AZD3839. This metabolic pathway was not foreseen on the basis of the obtained in vitro data. In conclusion, we discovered an unusual metabolic pathway of aryl-pyrimidine-containing compounds by a ring-opening reaction followed by elimination of a carbon atom and a ring closure to form an imidazole ring.

Improvement of endothelial function in a murine model of mild cholesterol-induced atherosclerosis by mineralocorticoid antagonism.

PubMed

Kratz, Mario T; Schirmer, Stephan H; Baumhäkel, Magnus; Böhm, Michael

2016-08-01

The renin-angiotensin-aldosterone-system (RAAS) plays a role in endothelial dysfunction and atherosclerosis. During treatment with RAAS-inhibitors, elevated aldosterone may sustain "aldosterone escape". We investigated the effects of treatment with the mineralocorticoid antagonist eplerenone (Ep) compared with ramipril (Rami) or the combination of both on oxidative stress, plaque formation and endothelial function, in atherosclerotic apolipoprotein E deficient mice (ApoE(-/-)-mice). ApoE(-/-)-mice were fed a cholesterol rich diet (21% fat, 19.5% casein, 1.25% cholesterol) for 8 weeks to produce mild atherosclerosis (i.e. plaque load 20-30%). ApoE(-/-)-mice (control), ApoE(-/-)-mice treated with Ep (25 mg/kg/day), Rami (2.5 mg/kg/day) and their combination were compared. Heart rate (HR) and blood pressure (BP) were measured using the tail-cuff-method. Endothelial function was measured in aortic rings and corpora cavernosal strips (CCs). Atherosclerotic plaque burden, collagen content, oxidative stress (Dihydroethidium (DHE) staining) and macrophages were determined. Treatments had no effects on HR and slightly reduced BP in ApoE(-/-)-mice treated with the combination of eplerenone and ramipril. Endothelium-dependent relaxation of aortic rings and CCs with carbachol was significantly improved in animals treated with Ep, Rami or their combination (p = 0.05 - p = 0.001). DHE-stained penile and aortic sections revealed a significant reduction in superoxide production in all treated groups (p = 0.035 - p = 0.001). In parallel, aortic and penile collagen content in ApoE(-/-)-mice was significantly decreased (p = 0.035 - p < 0.001) in animals treated with Ep, Rami or their combination. In agreement, there was a trend towards a reduction of aortic plaque area by treatment with Ep (-9.0 ± 3.2%) and Rami (-11.9 ± 4%). Only the treatment with the combination induced a significant reduction of the atherosclerotic plaque burden (p = 0.045). Moreover, the treatment of ApoE(-/-)-mice with Ep, Rami and their combination significantly reduced the count macrophage count in atherosclerotic plaque lesions. Ep restored endothelial function by reduction of oxidative stress, atherosclerotic macrophage content, atherosclerotic lesion size and fibrosis to the same extent as treatment with Rami or the combination. Mineralocorticoid antagonism provides vasculoprotective effects and should be clinically evaluated for vascular disease such as erectile dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase.

PubMed

Morwick, Tina; Büttner, Frank H; Cywin, Charles L; Dahmann, Georg; Hickey, Eugene; Jakes, Scott; Kaplita, Paul; Kashem, Mohammed A; Kerr, Steven; Kugler, Stanley; Mao, Wang; Marshall, Daniel; Paw, Zofia; Shih, Cheng-Kon; Wu, Frank; Young, Erick

2010-01-28

A highly selective series of bisbenzamide inhibitors of Rho-associated coiled-coil forming protein kinase (ROCK) and a related ureidobenzamide series, both identified by high throughput screening (HTS), are described. Details of the hit validation and lead generation process, including structure-activity relationship (SAR) studies, a selectivity assessment, target-independent profiling (TIP) results, and an analysis of functional activity using a rat aortic ring assay are discussed.

Syntheses of Thienylamphetamine Derivatives via Borane Chemistry

DTIC Science & Technology

1988-08-01

derivatives of aniline, benzylamines, and phenylethylamines . Their work, showed that, for ring-iodinated phenylalkylamines, brain uptake, reten- tion, and...intensify, mimic, or oppose the biological effect of the metabolite depending on the analogue’s affinity for the receptor site and its intrinsic...amphetamine They found no discernable Itflocano in the dr.4g effect in dogs and on isolated rabbit intestinal tp ho th~onasphet4aine was found to be

Nuclear Overhauser effect studies on the conformation of magnesium adenosine 5'-triphosphate bound to rabbit muscle creatine kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosevear, P.R.; Powers, V.M.; Dowhan, D.

1987-08-25

Nuclear Overhauser effects were used to determine interproton distances on MgATP bound to rabbit muscle creatine kinase. The internuclear distances were used in a distance geometry program that objectively determines both the conformation of the bound MgATP and its uniqueness. Two classes of structures were found that satisfied the measured interproton distances. Both classes had the same anti glycosidic torsional angle (X = 78 +/- 10/sup 0/) but differed in their ribose ring puckers (O1'-endo or C4'-exo). The uniqueness of the glycosidic torsional angle is consistent with the preference of creatine kinase for adenine nucleotides. One of these conformations ofmore » MgATP bound to creatine kinase is indistinguishable from the conformation found for Co(NH/sub 3/)/sub 4/ ATP bound to the catalytic subunit of protein kinase, which also has a high specificity for adenine nucleotides. Distance geometry calculations also suggest that upper limit distances, when low enough (less than or equal to 3.4 A), can be used instead of measured distances to define, within experimental error, the glycosidic torsional angle of bound nucleotides. However, this approach does not permit an evaluation of the ribose ring pucker.« less

Potassium Inhibits Dietary Salt-Induced Transforming Growth Factor-β Production

PubMed Central

Ying, Wei-Zhong; Aaron, Kristal; Wang, Pei-Xuan; Sanders, Paul W.

2009-01-01

Human and animal studies demonstrate an untoward effect of excess dietary NaCl (salt) intake on cardiovascular function and life span. The endothelium in particular augments the production of transforming growth factor (TGF)-β, a fibrogenic growth factor, in response to excess dietary salt intake. This study explored the initiating mechanism that regulates salt-induced endothelial cell production of TGF-β. Male Sprague-Dawley rats were given diets containing different amounts of NaCl and potassium for 4 days. A bioassay for TGF-β demonstrated increased (35.2%) amounts of active TGF-β in the medium of aortic ring segments from rats on the high-salt diet compared with rats maintained on a 0.3% NaCl diet. Inhibition of the large-conductance, calcium-activated potassium channel inhibited dietary salt-induced vascular production of TGF-β but did not affect production of TGF-β by ring segments from rats on the low-salt diet. Immunohistochemical and Western analyses demonstrated the α subunit of the calcium-activated potassium channel in endothelial cells. Increasing medium [K+] inhibited production of dietary salt-induced vascular production levels of total and active TGF-β but did not alter TGF-β production by aortic rings from rats on the 0.3% NaCl diet. Increasing dietary potassium content decreased urinary active TGF-β in animals receiving the high-salt diet but did not change urinary active TGF-β in animals receiving the low-salt diet. The findings demonstrated an interesting interaction between the dietary intake of potassium and excess NaCl and further showed the fundamental role of the endothelial calcium-activated potassium channel in the vascular response to excess salt intake. PMID:19738156

[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].

PubMed

Sievers, Hans H

2002-08-01

At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially if these are progressive and combined with aortic insufficiency. ROSS-OPERATION: The Ross-Operation includes the replacement of the diseased aortic valve with the pulmonary autograft and reconstruction of the right ventricular outflow tract using a homograft. The hemodynamic results are excellent regarding the autograft and also the clinical results with very low thromboembolic risk and acceptable reoperation rate. This method is especially indicated for active young patients, women, who desire children, athletes and patients in general, who like to avoid long-term anticoagulation. In some cases the homograft may develop a dysfunction predominantly a pulmonary stenosis requiring reoperation. In the author's series of 245 Ross-operations in 12 years the homograft had to be replaced in 4 cases without letality. Innovative, decellularized homografts with the potential to repopulate with autologeous cells show promising results after 1 year of clinical implantation without signs of antibody development. Probably these tissue-engineered modification may improve the homograft results. The reconstructive techniques of the aortic valve and the Ross-operation have a certain risk of reoperation that must be weighed against the advantages of very low hospital and late valve related death, excellent hemodynamics, very low risk of macro- and microembolism as well as bleeding, lack of long-term anticoagulation and unrestricted life-style.

The metabolites of cyclohexylamine in man and certain animals

PubMed Central

Renwick, A. G.; Williams, R. T.

1972-01-01

1. [1-14C]Cyclohexylamine hydrochloride was synthesized and given orally or intraperitoneally to rats, rabbits and guinea pigs (dose 50–500mg/kg) and orally to humans (dose 25 or 200mg/person). The 14C is excreted mainly in the urine, most of the excretion occurring in the first day after dosing. Only small amounts (1–7%) are found in the faeces. 2. In the rat, guinea pig and man, the amine is largely excreted unchanged, only 4–5% of the dose being metabolized in 24h in the rat and guinea pig and 1–2% in man. In the rabbit about two-thirds of the dose is excreted unchanged and about 30% is metabolized. 3. In the rat, five minor metabolites were found, namely cyclohexanol (0.05%), trans-3- (2.2%), cis-4- (1.7%), trans-4- (0.5%) and cis-3-aminocyclohexanol (0.1% of the dose in 24h). 4. In the rabbit, eight metabolites were identified, namely cyclohexanol (9.3%), trans-cyclohexane-1,2-diol (4.7%), cyclohexanone (0.2%), cyclohexylhydroxylamine (0.2%) and trans-3- (11.3%), cis-3- (0.6%), trans-4- (0.4%) and cis-4-aminocyclohexanol (0.2%). 5. In the guinea pig, six minor metabolites were found, namely cyclohexanol (0.5%), trans-cyclohexane-1,2-diol (2.5%) and trans-3- (1.2%), cis-3- (0.2%), trans-4- (0.2%) and cis-4-aminocyclohexanol (0.2%). 6. In man only two metabolites were definitely identified, namely cyclohexanol (0.2%) and trans-cyclohexane-1,2-diol (1.4% of the dose), but man had been given a smaller dose (3mg/kg) than the other species (50mg/kg). 7. The hydroxylated metabolites of cyclohexylamine were excreted in the urine in both free and conjugated forms. 8. Although cyclohexylamine is metabolized to only a minor extent, in rats the metabolism was mainly through hydroxylation of the cyclohexane ring, in man by deamination and in guinea pigs and rabbits by ring hydroxylation and deamination. PMID:4655821

Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques.

PubMed

Spadaccio, Cristiano; Nappi, Francesco; De Marco, Federico; Sedati, Pietro; Sutherland, Fraser W H; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto

2016-01-01

In this study, we tested in vivo effectiveness of a previously developed poly-l-lactide/poly-ε-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings.

Asymptomatic strut fracture in DeBakey-Surgitool aortic valves: incidence, management, and metallurgic aspects.

PubMed

Von Der Emde J, J; Eberlein, U; Breme J, J

1990-01-01

From August 1971 through November 1972, we implanted 62 Model 2 DeBakey-Surgitool aortic valve prostheses in 62 patients, 4 of whom later had clinically asymptomatic strut fractures. In 1 case, the patient died suddenly, and autopsy revealed detachment of the ball-cage; in each of the other 3 cases, fractures of 2 struts close to the base of the prosthesis were diagnosed fluoroscopically, and the patients underwent successful reoperation. The interval between implantation and reoperation ranged from 11 months to 16 years, 9 months. In 1 patient, retrospective study of chest radiographs revealed that the fracture had been present for 2(1/2) years. Larger valves (>/= A6) were affected significantly more often than smaller ones. We performed metallurgic analysis of 1 prosthesis: results revealed strut wear from fatigue cracking and secondary abrasion. Strut fracture was also promoted by suspension of the cage at right angles to the prosthetic ring and by use of a pyrolytic carbon ball in a titanium cage (i.e., an occluder harder than its holder). Patients with DeBakey-Surgitool aortic valve prostheses should undergo annual radiologic examinations to enable early detection of strut fractures. Prophylactic valve replacement is not indicated.

Evaluation of prosthetic valve obstruction on electrocardiographically gated multidetector-row computed tomography--identification of subprosthetic pannus in the aortic position.

PubMed

Ueda, Tomohiro; Teshima, Hideki; Fukunaga, Shuji; Aoyagi, Shigeaki; Tanaka, Hiroyuki

2013-01-01

This study was performed to evaluate the diagnostic role of electrocardiographically gated multidetector-row computed tomography (MDCT) for prosthetic valve obstruction (PVO) in the aortic position. Between 2002 and 2006, 9 patients were diagnosed with PVO of an aortic bileaflet mechanical valve based on echocardiographic and cineradiographic criteria. These 9 patients were examined using MDCT before replacement of the mechanical valve, and intraoperative findings were compared to morphologic periprosthetic abnormalities observed on MDCT. CT attenuation (Hounsfield units; HU) of the periprosthetic abnormalities was measured to investigate the underlying cause of the PVO. MDCT showed subprosthetic masses extending beyond the prosthetic ring into the orifice of the valve. At reoperation, presence of subprosthetic pannus was confirmed in all of the 9 patients, but no periprosthetic thrombus was found. The mean CT attenuation of the subprosthetic pannus was 170 HU, and it was significantly greater than that obtained from the interventricular septum (108 HU; P<0.0001). MDCT can be used to clearly visualize subprosthetic pannus causing PVO and the mean CT attenuation of subprosthetic pannus is significantly higher than that of the interventricular septum on MDCT.

Isolation and characterization of the progenitor cells from the blastema tissue formed at experimentally-created rabbit ear hole.

PubMed

Baghaban Eslaminejad, Mohamadreza; Bordbar, Sima

2013-02-01

Objective(s) : Throughout evolution, mammalians have increasingly lost their ability to regenerate structures however rabbits are exceptional since they develop a blastema in their ear wound for regeneration purposes. Blastema consists of a group of undifferentiated cells capable of dividing and differentiating into the ear tissue. The objective of the present study is to isolate, culture expand, and characterize blastema progenitor cells in terms of their in vitro differentiation capacity. Five New Zealand white male rabbits were used in the present study. Using a punching apparatus, a 4-mm hole was created in the animal ears. Following 4 days, the blastema ring which was created in the periphery of primary hole in the ears was removed and cultivated. The cells migrated from the blastema were expanded through 3 successive subcultures and characterized in terms of their potential differentiation, growth characteristics, and culture requirements. The primary cultures tended to be morphologically heterogeneous having spindly-shaped fibroblast-like cells as well as flattened cells. Fibroblast-like cells survived and dominated the cultures. These cells tended to have the osteogenic, chondrogenic, and adipogenic differentiation potentials. They were highly colonogenic and maximum proliferation was achieved when the cells were plated at density of 100 cells/cm2 in a medium which contained 10% fetal bovine serum (FBS). Taken together, blastema tissue-derived stem cells from rabbit ear are of mesenchymal stem cell-like population. Studies similar to this will assist scientist better understanding the nature of blastema tissue formed at rabbit ear to regenerate the wound.

Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals.

PubMed

Ojewole, J A O; Kamadyaapa, D R; Gondwe, M M; Moodley, K; Musabayane, C T

2007-01-01

The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001), negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left and spontaneously beating right atrial muscle preparations, respectively. Moreover, PAE reduced or abolished, in a concentration-dependent manner, the positive inotropic and chronotropic responses of guinea pig isolated atrial muscle strips induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM). PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from healthy normal Wistar rats. Like acetylcholine (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration-related relaxations of isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated, endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart rates of the anaesthetised normotensive and hypertensive rats used. The results of this laboratory animal study indicate that PAE caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of PAE was endothelium dependent, and was, therefore, possibly dependent on the synthesis and release of nitric oxide (NO). The vasorelaxant effects of PAE appeared to contribute significantly to the hypotensive (antihypertensive) effects of the plant extract. However, the findings of this study tend to suggest that P americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.

Role of protein sulfation in vasodilation induced by minoxidil sulfate, a K+ channel opener

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meisheri, K.D.; Oleynek, J.J.; Puddington, L.

Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that MNXS, 5 microM, but not the parent compound minoxidil, was a potent vasodilator. Whereas the relaxant effects of an another K+ channel opener vasodilator, BRL-34915 (cromakalim), were removed by washing with physiological saline solution, the effects of MNXS persisted after repeated washout attempts. Furthermore, after an initial exposure ofmore » segments of intact RMA to (35S) MNXS, greater than 30% of the radiolabel was retained 2 hr after removal of the drug. In contrast, retention of radiolabel was not detected with either (3H)MNXS (label on the piperidine ring of MNXS) or (3H)minoxidil (each less than 3% after a 2-hr washout). These data suggested that the sulfate moiety from MNXS was closely associated with the vascular tissue. To determine if proteins were the acceptors of sulfate from MNXS, intact RMAs were incubated with (35S)MNXS, and then 35S-labeled proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by fluorography. Preferential labeling of a 116 kD protein was detected by 2 and 5 min of treatment. A 43 kD protein (resembling actin) also showed significant labeling. A similar profile of 35S-labeled proteins was observed in (35S) MNXS-treated A7r5 rat aortic smooth muscle cells, suggesting that the majority of proteins labeled by (35S)MNXS in intact RMA were components of smooth muscle cells.« less

High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

PubMed Central

Almabrouk, Tarek A. M.; White, Anna D.; Ugusman, Azizah B.; Skiba, Dominik S.; Katwan, Omar J.; Alganga, Husam; Guzik, Tomasz J.; Touyz, Rhian M.; Salt, Ian P.; Kennedy, Simon

2018-01-01

Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later. Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice. Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD. PMID:29479319

Ca2+ mobilization in the aortic endothelium in streptozotocin-induced diabetic and cholesterol-fed mice.

PubMed

Kamata, K; Nakajima, M

1998-04-01

1. Experiments were performed to compare Ca2+ mobilization in the aortic endothelium in streptozotocin (STZ)-induced diabetic and cholesterol-fed mice with that in age-matched controls. 2. The intracellular free Ca2+ ([Ca2+]i) in the fura PE-3 loaded endothelium of aortic rings was dose-dependently increased by cumulative administration of acetylcholine (ACh). ACh caused a transient rise in [Ca2+]i in Ca2+-free medium. The ACh-induced increase in [Ca2+]i in normal or Ca2+-free medium was significantly weaker in both STZ-induced diabetic and cholesterol-fed mice. 3. The weaker [Ca2+]i response in Ca2+-containing medium in STZ-induced diabetic and cholesterol-fed mice was normalized by chronic administration of cholestyramine. 4. The increased low density lipoprotein (LDL) levels seen in both STZ-induced diabetic and cholesterol-fed mice were normalized by the same chronic administration of cholestyramine (300 mg kg(-1), p.o. daily for 10 weeks). Chronic administration of cholestyramine had no effect on the plasma glucose level. 5. Lysophosphatidylcholine (LPC) decreased the [Ca2+]i responses to ACh in the aortic endothelium from normal mice. 6. These results suggest that ACh increases both Ca2+ influx and Ca2+ release from storage in the aortic endothelium. The weaker [Ca2+]i influx seen in the endothelium of aortae from both STZ-induced diabetic and cholesterol-fed mice was improved by the chronic administration of cholestyramine, and we suggest that this improvement is due, at least in part, to a lowering of the plasma LDL level. It is further suggested that LPC may have an important influence over Ca2+ mobilization in the endothelium.

Supravalvar mitral ring with a parachute mitral valve and subcoarctation of the aorta in a child with hemodynamically significant VSD. A study of the morphology, echocardiographic diagnostics and surgical therapy.

PubMed

Mądry, Wojciech; Karolczak, Maciej A; Grabowski, Krzysztof

2017-09-01

The authors present a case of echocardiographic diagnosis of supravalvar mitral ring (a fibromembranous structure that arose from the atrial surface of the mitral leaflets) in a child with a parachute mitral valve, a ventricular septal defect, and mild narrowing of the aortic isthmus. The supravalvar mitral stenosis is a typical but very infrequently detected element of the complex of anatomical abnormalities located within the left heart and the proximal aorta, called the Shone's complex (syndrome). Diagnosing an additional, hemodynamically significant anatomic defect during echocardiography was possible thanks to the detection of marked mobility limitation of the ring-adjacent part of the mitral valve mural leaflet as well as of an atypical image of turbulence occurring during the inflow from the left atrium to the left ventricle. The early diagnosis made it possible to perform complete correction of this complex congenital defect within a single operation.

Treponema pallidum Invades Intercellular Junctions of Endothelial Cell Monolayers

NASA Astrophysics Data System (ADS)

Thomas, D. Denee; Navab, Mahamad; Haake, David A.; Fogelman, Alan M.; Miller, James N.; Lovett, Michael A.

1988-05-01

The pathogenesis of syphilis reflects invasive properties of Treponema pallidum, but the actual mode of tissue invasion is unknown. We have found two in vitro parallels of treponemal invasiveness. We tested whether motile T. pallidum could invade host cells by determining the fate of radiolabeled motile organisms added to a HeLa cell monolayer; 26% of treponemes associated with the monolayer in a trypsin-resistant niche, presumably between the monolayer and the surface to which it adhered, but did not attain intracellularity. Attachment of T. pallidum to cultured human and rabbit aortic and human umbilical vein endothelial cells was 2-fold greater than to HeLa cells. We added T. pallidum to aortic endothelial cells grown on membrane filters under conditions in which tight intercellular junctions had formed. T. pallidum was able to pass through the endothelial cell monolayers without altering tight junctions, as measured by electrical resistance. In contrast, heat-killed T. pallidum and the nonpathogen Treponema phagedenis biotype Reiter failed to penetrate the monolayer. Transmission electron micrographs of sections of the monolayer showed T. pallidum in intercellular junctions. Our in vitro observations suggest that these highly motile spirochetes may leave the circulation by invading the junctions between endothelial cells.

The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

PubMed Central

Kalsner, S

1976-01-01

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue. PMID:974389

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOSmore » and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced vascular dysfunction. • Arsenic reduced ACh-induced aortic relaxation but didn’t alter response to SNP and PE. • Arsenic affected aortic NO signalling and production of inflammatory mediators. • Arsenic produced vasculopathic lesions in aorta. • Atorvastatin restored arsenic-induced functional, biochemical and structural changes.« less

Calcium-dependent mechanisms mediate the vasorelaxant effects of Tridax procumbens (Lin) aqueous leaf extract in rat aortic ring.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Yemitan, Omoniyi K; Murtala, Babatunde A; Alada, Abdul-Rasak A

2014-05-01

Tridax procumbens leaf extract has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant effect on smooth muscles. The present study was designed to investigate the role of calcium in the vasorelaxant effect of this extract. Concentration-response studies with noradrenaline (NA), KCl and CaCl2 were carried out in rat aortic rings with and without the extract in physiological salt solution (PSS) (n=6 each). Also, the role of intracellular calcium mobilization was studied by measuring the phasic response to NA in Ca2+-free N,N-ethylene glycol tetraacetic acid (EGTA) PSS (n=6). The results showed that the contractile responses to either NA or KCl were attenuated (p<0.05) in the presence of the extract. Also, the extract attenuated the contractile response to CaCl2 in the presence of NA or KCl (p<0.05) in the Ca2+-free EGTA PSS, while the phasic response to NA was significantly (p<0.05) diminished. These results suggest that the vasorelaxant effect of T. procumbens leaf extract may be mediated by a non-specific, non-competitive inhibition of Ca2+ influx as well as by inhibition of Ca2+ mobilization from intracellular stores. This implies that it may contain vasorelaxant agents that may have calcium antagonistic potential.

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through NO and Akt

PubMed Central

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J.

2011-01-01

Objective Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous NO synthase (NOS) inhibitors ADMA and L-NMMA. This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA independent effects that influence endothelial function. Methods and Results Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in HUVEC, we found that DDAH1 acts to promote endothelial cell proliferation, migration and tube formation both by Akt phosphorylation as well as through the traditional role of degrading ADMA. Incubation of HUVEC with the NOS inhibitors L-NAME or ADMA, the soluble guanylyl cyclase inhibitor ODQ, or the cGMP analog 8-pCPT-cGMP had no effect on p-AktSer473, indicating that the increase of p-AktSer473 produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase of p-AktSer473. Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. Conclusions DDAH1 exerts a unique role in activating Akt that affects endothelial function independent of degrading endogenous NOS inhibitors. PMID:21212404

Green synthesis of silver nanoparticles using Achillea biebersteinii flower extract and its anti-angiogenic properties in the rat aortic ring model.

PubMed

Baharara, Javad; Namvar, Farideh; Ramezani, Tayebe; Hosseini, Nasrin; Mohamad, Rosfarizan

2014-04-15

Silver nanoparticles display unique physical and biological properties which have attracted intensive research interest because of their important medical applications. In this study silver nanoparticles (Ab.Ag-NPs) were synthesized for biomedical applications using a completely green biosynthetic method using Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs were investigated using UV-visible spectroscopic techniques, transmission electron microscopy (TEM), zeta potential and energy dispersive X-ray spectrometers (EDS). The UV-visible spectroscopic analysis showed the absorbance peak at 460 nm, which indicates the synthesis of silver nanoparticles. The average particle diameter as determined by TEM was found to be 12±2 nm. The zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis also exhibits presentation of silver element. As angiogenesis is an important phenomenon and as growth factors imbalance in this process causes the acceleration of several diseases including cancer, the anti-angiogenic properties of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed that Ab.Ag-NPs (200 μg/mL) lead to a 50% reduction in the length and number of vessel-like structures. The synthesized silver nanoparticles from the Achillea biebersteinii flowers extract, which do not involve any harmful chemicals were well-dispersed and stabilized through this green method and showed potential therapeutic benefits against angiogenesis.

Investigation of terpinen-4-ol effects on vascular smooth muscle relaxation.

PubMed

Maia-Joca, Rebeca Peres Moreno; Joca, Humberto Cavalcante; Ribeiro, Francisca Jéssica Penha; do Nascimento, Renata Vieira; Silva-Alves, Kerly Shamyra; Cruz, Jader S; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2014-10-12

This study investigated the mechanisms underlying the vascular effects of terpinen-4-ol in isolated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by terpinen-4-ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, terpinen-4-ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbol 12,13-dibutyrate (1 μM). Terpinen-4-ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by terpinen-4-ol exposure. The present results suggest that terpinen-4-ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through voltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.

Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity

PubMed Central

Knock, Greg A.; Mahn, Katharina; Mann, Giovanni E.; Ward, Jeremy P.T.; Aaronson, Philip I.

2018-01-01

We examined the effects of dietary soy on the contributions of endothelium-derived hyperpolarising factor (EDHF), nitric oxide (NO), and oxidative stress to vascular tone in isolated aortic rings and small mesenteric and pulmonary arteries in vitro. Male Wistar rats were either continuously fed a soy-deficient diet (SD) or switched from a soy-deficient diet to a soy-rich one for 6 months (SW). Contractile responses were generally smaller in arteries from SW rats. In mesenteric arteries, this difference was blunted by L-NAME, but not by charybdotoxin and apamin. Preconstricted SW mesenteric arteries were more sensitive to acetylcholine (ACh) than SD ones. This difference was unaffected by L-NAME but was abolished by charybdotoxin and apamin. Exogenous superoxide dismutase (SOD) and catalase induced powerful relaxations in aortic rings, which were smaller in those from SW rats. In mesenteric and pulmonary arteries, however, they partially inhibited ACh-mediated relaxation, and enhanced PGF2α–mediated contraction, respectively. Our results suggest that feeding aging male rats a soy-rich diet results in improved agonist-mediated EDHF production and a generalized reduction in contractile force, which is partly due to elevated basal NO. Our data also suggest a prorelaxant role for endogenous H2O2 in small arteries, which is modulated by a soy diet. PMID:16895793

Potentiation of vasoconstriction and pressor response by low concentration of monomethylarsonous acid (MMA(III)).

PubMed

Lim, Kyung-Min; Shin, Yoo-Sun; Kang, Seojin; Noh, Ji-Yoon; Kim, Keunyoung; Chung, Seung-Min; Yun, Yeo-Pyo; Chung, Jin-Ho

2011-09-10

A close link between arsenic exposure and hypertension has been well-established through many epidemiological reports, yet the mechanism underlying it remains unclear. Here we report that nanomolar concentrations of monomethylarsonous acid (MMA(III)), a toxic trivalent methylated arsenic metabolite, can potentiate agonist-induced vasoconstriction and pressor responses. In freshly isolated rat aortic ring, exposure to nanomolar MMA(III) (100-500 nM) potentiated phenylephrine (PE)-induced vasoconstriction while at higher concentrations (≥2.5 μM), suppression of vasoconstriction and apoptosis of vascular smooth muscle were observed. Potentiation of agonist-induced vasoconstriction was also observed with other contractile agonists and it was retained in endothelium-denuded aortic rings, suggesting that these events are agonist-independent and smooth muscle cell dependent. Interestingly, exposure to MMA(III) resulted in increased myosin light chain phosphorylation while PE-induced Ca2+ influx was not affected, reflecting that Ca2+ sensitization is involved. In line with this, MMA(III) enhanced agonist-induced activation of small GTPase RhoA, a key contributor to Ca2+ sensitization. Of note, treatment of MMA(III) to rats induced significantly higher pressor responses in vivo, demonstrating that this event can occur in vivo indeed. We believe that RhoA-mediated Ca2+ sensitization and the resultant potentiation of vasoconstriction by MMA(III) may shed light on arsenic-associated hypertension. Copyright © 2011. Published by Elsevier Ireland Ltd.

3D analysis of vortical structures in an abdominal aortic aneurysm by stereoscopic PIV

NASA Astrophysics Data System (ADS)

Deplano, Valérie; Guivier-Curien, Carine; Bertrand, Eric

2016-11-01

The present work presents an experimental in vitro three-dimensional analysis of the flow dynamics in an abdominal aortic aneurysm (AAA) through stereoscopic particle image velocimetry (SPIV) measurements. The experimental set-up mimics the pathophysiological context involving a shear thinning blood analogue fluid, compliant AAA and aorto-iliac bifurcation walls and controlled inlet and outlet flow rate and pressure waveforms as well as working fluid temperature. SPIV was carefully calibrated and conducted to assess the three velocity components in the AAA volume. For the first time in the literature, the 3D vortex ring genesis, propagation, and vanishing in the AAA bulge are experimentally described and quantified. In comparison with classical 2-component PIV measurements (2C PIV), the third component of the velocity vector was shown to be of importance in such a geometry, especially, during the deceleration phase of the flow rate. The 3D velocity magnitude reached up more than 20 % of the 2D one showing that 2C PIV are definitively not accurate enough to provide a complete description of flow behaviour in an AAA. In addition to potential clinical implications of a full 3D vortex ring description in AAA evolution, the 3D in vitro experimental quantification of the flow dynamics carried out in the present study offers an interesting tool for the validation of fluid-structure interaction numerical studies dealing with AAA.

Multi-Carotenoids at Physiological Levels Inhibit VEGF-Induced Tube Formation of Endothelial Cells and the Possible Mechanisms of Action Both In Vitro and Ex Vivo.

PubMed

Huang, Chien-Hao; Huang, Chin-Shiu; Hu, Miao-Lin; Chuang, Cheng-Hung

2018-01-01

Carotenoids have been shown to exhibit antiangiogenic activities. Several studies have indicated that carotenoids used in combination were more effective on antioxidation and anticancer actions than carotenoids used singly. However, it is unclear whether multi-carotenoids have antiangiogenic effects. We investigated the effects of multi-carotenoids at physiological plasma levels of Taiwanese (abbreviated as MCT, with a total of 1.4 μM) and Americans (abbreviated as MCA, with a total of 1.8 μM), and of post-supplemental plasma levels (abbreviated as HMC with a total of 3.55 μM) on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vein endothelial cells (HUVECs) and rat aortic rings. MCT, MCA, and HMC inhibited VEGF-induced migration, invasion, and tube formation of HUVECs as well as new vessels formation in rat aortic rings. MCT, MCA, and HMC inhibited activities o\\f matrix metalloproteinase (MMP)-2, urokinase plasminogen activator, and phosphorylation of VEGF receptor 2 induced by VEGF. Moreover, MCT, MCA, and HMC significantly upregulated protein expression of tissue inhibitors of MMP-2 and plasminogen activator inhibitor-1. These results demonstrate the antiangiogenic effect of multi-carotenoids both in vitro and ex vivo with possible mechanistic actions involving attenuation of VEGF receptor 2 phosphorylation and extracellular matrix degradation.

Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein Inhibition.

PubMed

Wu, Ben J; Li, Yue; Ong, Kwok L; Sun, Yidan; Shrestha, Sudichhya; Hou, Liming; Johns, Douglas; Barter, Philip J; Rye, Kerry-Anne

2017-12-01

Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia. New Zealand White rabbits received normal chow or chow supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery endothelial denudation and bare metal steel stent deployment were performed after 2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks poststent deployment. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and increased plasma apolipoprotein A-I and HDL cholesterol levels by 53±6.3% and 120±19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro-anacetrapib treatment reduced the intimal area of the stented arteries by 43±5.6% ( P <0.001), the media area was unchanged, and the arterial lumen area increased by 12±2.4% ( P <0.05). Des-fluoro-anacetrapib treatment inhibited vascular smooth muscle cell proliferation by 41±4.5% ( P <0.001). Incubation of isolated HDLs from des-fluoro-anacetrapib-treated animals with human aortic smooth muscle cells at apolipoprotein A-I concentrations comparable to their plasma levels inhibited cell proliferation and migration. These effects were dependent on scavenger receptor-B1, the adaptor protein PDZ domain-containing protein 1, and phosphatidylinositol-3-kinase/Akt activation. HDLs from des-fluoro-anacetrapib-treated animals also inhibited proinflammatory cytokine-induced human aortic smooth muscle cell proliferation and stent-induced vascular inflammation. Inhibiting cholesteryl ester transfer protein activity in New Zealand White rabbits with iliac artery balloon injury and stent deployment increases HDL levels, inhibits vascular smooth muscle cell proliferation, and reduces neointimal hyperplasia in an scavenger receptor-B1, PDZ domain-containing protein 1- and phosphatidylinositol-3-kinase/Akt-dependent manner. © 2017 American Heart Association, Inc.

Measurement of drug and macromolecule diffusion across atherosclerotic rabbit aorta ex vivo by attenuated total reflection-Fourier transform infrared imaging

NASA Astrophysics Data System (ADS)

Palombo, Francesca; Danoux, Charlène B.; Weinberg, Peter D.; Kazarian, Sergei G.

2009-07-01

Diffusion of two model drugs-benzyl nicotinate and ibuprofen-and the plasma macromolecule albumin across atherosclerotic rabbit aorta was studied ex vivo by attenuated total reflection-Fourier transform infrared (ATR-FTIR) imaging. Solutions of these molecules were applied to the endothelial surface of histological sections of the aortic wall that were sandwiched between two impermeable surfaces. An array of spectra, each corresponding to a specific location in the section, was obtained at various times during solute diffusion into the wall and revealed the distribution of the solutes within the tissue. Benzyl nicotinate in Ringer's solution showed higher affinity for atherosclerotic plaque than for apparently healthy tissue. Transmural concentration profiles for albumin demonstrated its permeation across the section and were consistent with a relatively low distribution volume for the macromolecule in the middle of the wall. The ability of albumin to act as a drug carrier for ibuprofen, otherwise undetected within the tissue, was demonstrated by multivariate subtraction image analysis. In conclusion, ATR-FTIR imaging can be used to study transport processes in tissue samples with high spatial and temporal resolution and without the need to label the solutes under study.

Resveratrol shows vasoprotective effect reducing oxidative stress without affecting metabolic disturbances in insulin-dependent diabetes of rabbits.

PubMed

Akar, Fatma; Pektas, M Bilgehan; Tufan, Can; Soylemez, Selen; Sepici, Aylin; Ulus, A Tulga; Gokalp, Burcu; Ozturk, Kamile; Surucu, H Selcuk

2011-04-01

Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes. Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits. Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes. Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.

Advanced technologies for cardiac valvular replacement, transcatheter innovations and reconstructive surgery.

PubMed

Jamieson, W R Eric

2006-01-01

Since the 2002 Surgical Technology International monograph on valvular prostheses, there have been significant developmental and investigative advances. Aortic bioprostheses and mechanical prostheses have undergone design changes to optimize hemodynamics and prevent patient-prosthesis mismatch to have a potential satisfactory influence on survival. There has been continual technological improvements striving to bring forward advances that improve the durability of bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also has been a continuance to preserve biological tissue with glutaraldehyde, rather than clinically evaluate other cross-linking technologies, by controlling or retarding calcification with therapies to control phospholipids and residual aldehydes. The techniques of mitral valve reconstruction have now been well established and new annuloplasty rings have been designed for the potential of maintaining the anatomical and physiological characteristics of the mitral annulus. Several objectives exist for annuloplasty, namely remodeling of the length and shape of the dilated annulus, prevention of dilatation of the annulus, and support for the potentially fragile area after partial-leaflet resection. Currently, there exists an emergence of catheter-based therapies for management of aortic stenosis and mitral regurgitation. For management of selected populations with critical aortic stenosis, techniques for aortic valve substitution have been developed for both antegrade and retrograde catheter techniques, as well as apical transventricular implantation. Mitral regurgitation has been addressed by experimental transcoronary sinus, stent-like devices and transventricular, edge-to-edge leaflet devices. The devices, descriptions and pictorial images comprise this monograph.

Inhibition of carboxylesterases by benzil (diphenylethane-1,2-dione) and heterocyclic analogues is dependent upon the aromaticity of the ring and the flexibility of the dione moiety.

PubMed

Hyatt, Janice L; Stacy, Vanessa; Wadkins, Randy M; Yoon, Kyoung Jin P; Wierdl, Monika; Edwards, Carol C; Zeller, Matthias; Hunter, Allen D; Danks, Mary K; Crundwell, Guy; Potter, Philip M

2005-08-25

Benzil has been identified as a potent selective inhibitor of carboxylesterases (CEs). Essential components of the molecule required for inhibitory activity include the dione moiety and the benzene rings, and substitution within the rings affords increased selectivity toward CEs from different species. Replacement of the benzene rings with heterocyclic substituents increased the K(i) values for the compounds toward three mammalian CEs when using o-nitrophenyl acetate as a substrate. Logarithmic plots of the K(i) values versus the empirical resonance energy, the heat of union of formation energy, or the aromatic stabilization energy determined from molecular orbital calculations for the ring structures yielded linear relationships that allowed prediction of the efficacy of the diones toward CE inhibition. Using these data, we predicted that 2,2'-naphthil would be an excellent inhibitor of mammalian CEs. This was demonstrated to be correct with a K(i) value of 1 nM being observed for a rabbit liver CE. In addition, molecular simulations of the movement of the ring structures around the dione dihedral indicated that the ability of the compounds to inhibit CEs was due, in part, to rotational constraints enforced by the dione moiety. Overall, these studies identify subdomains within the aromatic ethane-1,2-diones, that are responsible for CE inhibition.

Interaction in endothelium of non-muscular myosin light-chain kinase and the NF-κB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.

PubMed

Recoquillon, Sylvain; Carusio, Nunzia; Lagrue-Lakhal, Anne-Hélène; Tual-Chalot, Simon; Filippelli, Amelia; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2015-10-01

During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed in vitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies. © 2015 Authors; published by Portland Press Limited.

Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1.

PubMed

Jiang, Rujia; Hodgson, Jonathan M; Mas, Emilie; Croft, Kevin D; Ward, Natalie C

2016-01-01

Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes of De Vega versus biodegradable ring annuloplasty in the surgical treatment of tricuspid regurgitation (mid-term results).

PubMed

Basel, Halil; Aydin, Unal; Kutlu, Hakan; Dostbil, Aysenur; Karadag, Melike; Odabasi, Dolunay; Aydin, Cemalettin

2010-08-01

The aim of this study was to compare De Vega semicircular annuloplasty and a new biodegradable ring annuloplasty technique in patients requiring surgical intervention for tricuspid valve disease with concomitant disease of the mitral valve. Between January 2004 and May 2008, 129 consecutive patients underwent annuloplasty procedures to correct tricuspid valve regurgitation during a concomitant mitral valve operation requiring replacement. Additionally, 24 patients underwent aortic valve replacement (AVR), 11 underwent coronary artery bypass grafting (CABG), 5 underwent AVR plus CABG, 3 underwent mitral valve replacement plus atrial septal defect (ASD) closure, and 2 underwent ASD closure. The patients in this study were assigned to 2 groups: Kalangos ring annuloplasty was performed in 67 patients (group 1), and De Vega semicircular annuloplasty was performed in the remaining 62 patients (group 2). Both tricuspid valve repair techniques produced a low rate of complications; however, the number of patients who developed residual tricuspid regurgitation was significantly lower in group 1. The biodegradable ring annuloplasty technique may be used easily and safely in moderate and severe cases of tricuspid regurgitation; however, larger clinical series are necessary to confirm our promising results.

Experimental use of new absorbable tracheal stent.

PubMed

Schopf, Luciano F; Fraga, José Carlos; Porto, Rodrigo; Santos, Luis A; Marques, Douglas R; Sanchez, Paulo R; Meyer, Fabíola S; Ulbrich, Jane M

2017-11-16

Silicone and metallic stents are not effective in children with tracheobronchial stenosis or tracheomalacia. Herein, we aimed to evaluate the clinical manifestations and histological reaction of rabbit trachea to the presence of a new poly(lactic-co-glycolic acid) with polyisoprene (PLGA/PI) polymer absorbable stent. Fourteen adult white rabbits (weight, 3.0-3.5kg) were randomly assigned to three groups: Group I (n=6): PLGA/PI spiral stent; Group II (n=6): PLGA/PI fragment; and Group III (n=2): controls. After a longitudinal incision on three cervical tracheal rings, the stents and fragments were inserted into the trachea and fixed onto the lateral wall with nonabsorbable sutures. The stented group showed significantly more stridor at rest (p=0.0041), agitation (p=0.014), and use of accessory muscles (p=0.0002) and required more emergency endoscopies than the fragment group. Further, it showed significantly more remarkable histological inflammatory damage than the fragment and control groups (p=0.002). The new PLGA/PI polymeric stent implanted into the trachea of rabbits caused more clinical manifestations and histologically verified inflammatory reaction than the PLGA/PI polymeric fragment. Future studies should be aimed at reducing the stent-wall thickness. Copyright © 2017 Elsevier Inc. All rights reserved.

Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques

PubMed Central

Spadaccio, Cristiano; Nappi, Francesco; De Marco, Federico; Sedati, Pietro; Sutherland, Fraser W.H.; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto

2016-01-01

In this study, we tested in vivo effectiveness of a previously developed poly-l-lactide/poly-ε-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings. PMID:26949333

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

PubMed Central

Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

2015-01-01

Background Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI). Methods Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured. Results DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05). Conclusion After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels. PMID:25973795

In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent

PubMed Central

Botnar, René M.; Perez, Alexandra S.; Witte, Sonia; Wiethoff, Andrea J.; Laredo, James; Hamilton, James; Quist, William; Parsons, Edward C.; Vaidya, Anand; Kolodziej, Andrew; Barrett, John A.; Graham, Philip B.; Weisskoff, Robert M.; Manning, Warren J.; Johnstone, Michael T.

2010-01-01

Background Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis. Methods and Results Fifteen male New Zealand White rabbits (weight, ≈3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell’s viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as “hot spots” after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology. Conclusions We demonstrate the feasibility of in vivo “molecular” MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke. PMID:15066940

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring.

PubMed

Li, Chunxiao; Ning, Meiying; Yao, Xiaodong; Wang, Yankun; Liu, Ying

2016-09-01

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring (IVR) formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80°C for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldn't interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76χ+5.44 (r=0.9998), performing zero-order release at about the target dose of 60 µg/day over 21 days. Drug release increased with temperature elevating from 45 to 55°C, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well.

An investigation of the antiplatelet effects of succinobucol (AGI-1067).

PubMed

Houston, Stephanie A; Ugusman, Azizah; Gnanadesikan, Sukanya; Kennedy, Simon

2017-05-01

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet-platelet and platelet-vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10 -5 -10 -4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress.

In vitro degradation of hexanitrohexaazaisowurtzitane (CL-20) by cytosolic enzymes of Japanese quail and the rabbit.

PubMed

Bardai, Ghalib K; Halasz, Annamaria; Sunahara, Geoffrey I; Dodard, Sabine; Spear, Philip A; Grosse, Stephan; Hoang, Johnston; Hawari, Jalal

2006-12-01

Hexanitrohexaazaisowurtzitane (CL-20) is a polycyclic nitramine explosive and propellant, currently being considered as a potential replacement for existing cyclic nitramine explosives. Earlier studies have provided evidence suggestive of adverse liver effects in adult Coturnix spp. exposed to CL-20, yet analysis of tissue samples (plasma, liver, brain, heart, or spleen) indicated that CL-20 was not detectable in these treated animals. The present study was conducted to identify and purify the enzymes capable of CL-20 biotransformation. Results indicate that the hepatic biotransformation of CL-20 in vitro was inhibited by ethacrynic acid (93%) and by the glutathione (GSH) analogue S-octylglutathione (80%), suggesting the involvement of glutathione-S-transferase (GST). Partially purified cytosolic alpha- and mu-type GST (requiring presence of GSH as a cofactor) from quail and rabbit liver was capable of CL-20 biotransformation. The degradation of CL-20 (0.30 +/- 0.05 and 0.40 +/- 0.02 nmol/min/mg protein for quail and rabbit, respectively) was accompanied with the formation of nitrite and consumption of GSH. Using liquid chromatography/mass spectrometry, we detected two intermediates, that is, open-ring, monodenitrated GSH-conjugated CL-20 biotransformation product with the same deprotonated molecular mass ion at 699 Da, suggesting isomeric forms of the intermediate metabolites. Identity of the conjugated metabolites was confirmed by using ring-labeled [15N]CL-20 and the nitro group-labeled [15NO2]CL-20. These data suggest that the in vitro biotransformation of CL-20 by GST under the conditions tested may be a key initial step in the in vivo degradation of CL-20 in the quail and resulted in the formation of more biologically reactive intermediates than the parent compound. These data will aid in our understanding of the biotransformation processes of CL-20 in vivo.

Virgin Coconut Oil Prevents Blood Pressure Elevation and Improves Endothelial Functions in Rats Fed with Repeatedly Heated Palm Oil

PubMed Central

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil. PMID:23861707

Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

PubMed

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

[Vasodilator effect mediated by nitric oxide of the Zea mays L (andean purple corn) hydroalcoholic extract in aortic rings of rat].

PubMed

Moreno-Loaiza, Oscar; Paz-Aliaga, Azael

2010-01-01

To evaluate the vasodilator response of the hydroalcoholic extract of Zea mays L. (Andean purple corn) and to determine if this response is mediated by nitric oxide (NO). We obtained an extract by maceration for eight days of Andean purple corn cobs in 70% ethanol and subsequent concentration of the product. Thoracic aortic rings were evaluated in an isolated organ chamber, bathed with Krebs-Hensleit solution (KH), and vasomotor activity was recorded with an isometric tension transducer. Basal contraction was produced with 120 mM KCl and then, we proceeded to determinate the vasodilator effect of 3 doses of the extract: 0.1, 0.5, and 1.0 mg/mL. We used L-NG-Nitroarginin methyl ester (L-NAME) to verify that the vasodilation depends on nitric oxide sinteasa (NOs). Then we compared the inhibition of vascular contraction after incubation for 30 minutes, with purple corn extract and captopril 10-5 M. We observed a reduction in maximum contraction (100%) to 85.25 ± 2.60%, 77.76 ± 3.23%, and 73.3 ± 4.87% for doses of 0.1, 0.5 and 1,0 mg/mL respectively. The vasodilation was inhibited by prior incubation with L-NAME. Andean purple corn extract did not inhibit vascular contraction as captopril did (reduction to 75.27 ± 8.61%). The hydroalcoholic extract of Zea mays L produces NO dependent vasodilation.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

PubMed

Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

2018-06-01

Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

Honey promotes angiogeneic activity in the rat aortic ring assay.

PubMed

Rossiter, K; Cooper, A J; Voegeli, D; Lwaleed, B A

2010-10-01

To investigate possible effects of honey on angiogenesis, using in vitro analogues of angiogenesis and an endothelial proliferation assay. Using an in vitro rat aortic ring assay we compared pseudotubule formation by medicinal honey (Activon), supermarket honey (Rowse) and a honey-based ointment (Mesitran), with that of artificial honey (70% w/w sugar glucose/fructose). Pseudotubules were analysed using TCS Cellworks AngioSys software. The Angiokit sytem was used to validate the results. Using the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium. Bromide] assay, toxicity was also assessed on human umbilical vein endothelial cells (HUVEC) directly adherent to plastic. All honey preparations stimulated pseudotubule formation, maximal at around 0.2% honey. Medicinal honeys were more active than Rowse. The effect was not attributable to the sugar content. Among the honeys tested, the Manuka-based Activon preparation reduced residual viable biomass compared with a sugar control at > 0.32% v/v concentration. Rowse had a similar effect only at 2.5%, the highest dose tested. The influence of honey constituents on angiogenesis in a wound dressing context is likely to be positive, but would depend on the effective dilution of the honey and the penetration of the active constituents against an osmotic gradient. The extent to which this occurs has yet to be established. This work was conceived, designed and executed by the authors. Medical honey preparations were supplied unconditionally but free of charge by the distributors.

Esophageal dysfunction in four alpaca crias and a llama cria with vascular ring anomalies.

PubMed

McKenzie, Erica C; Seguin, Bernard; Cebra, Christopher K; Margiocco, Marco L; Anderson, David E; Löhr, Christiane V

2010-08-01

3 alpaca crias and cadavers of an alpaca cria and a llama cria were evaluated for evidence of esophageal dysfunction. All 5 crias were between 3 and 5 months of age when clinical signs developed, and all had a thin body condition when examined. Clinical signs included coughing, regurgitation, and grossly visible esophageal peristaltic waves. A barium esophagram was used to diagnose esophageal obstruction, megaesophagus, and a vascular ring anomaly (VRA). Fluoroscopy was used to evaluate deglutition, esophageal peristalsis, and the extent of esophageal dilation in 1 alpaca cria. A persistent right aortic arch was identified in 1 alpaca cria, and a left aortic arch with right ductus arteriosus or ligamentum arteriosum and an aberrant right subclavian artery were identified in the 4 remaining crias. Surgical correction of the VRA was attempted in the 3 live alpaca crias. It was complicated by the conformation and location of each VRA and inaccurate anatomic diagnosis of the VRAs before surgery. Treatment was universally unsuccessful because of intraoperative complications and the persistence of clinical signs after surgery. Megaesophagus is typically an idiopathic condition in camelids. However, these findings suggested that camelids with esophageal dysfunction during the neonatal period may have a VRA. The prognosis is grave for camelids with VRA, and accurate anatomic diagnosis of the VRA via the use of advanced imaging techniques (eg, angiography, computed tomography, or magnetic resonance imaging) may improve the success of surgical intervention.

The oxidation of cystamine and homocystamine by mammalian enzymes

PubMed Central

Bergeret, Bernadette; Blaschko, H.

1957-01-01

The oxidative deamination of cystamine and homocystamine by mammalian oxidases has been studied. The histaminase of pig kidney oxidizes homocystamine much more slowly than cystamine. The amine oxidase of mammalian liver (guinea-pig, rabbit) oxidizes homocystamine more rapidly than cystamine. Both amines are oxidized by plasma (or serum) of ruminants (ox, sheep, goat) and of the horse. In the enzymatic oxidation of homocystamine both aminogroups are removed; there is no evidence that a ring compound analogous to cystaldimine is accumulating. PMID:13489183

Prehistoric Agricultural Communities in West Central Alabama. Volume 1. Excavations in the Lubbub Creek Archaeological Locality.

DTIC Science & Technology

1983-01-01

hydrodynamic order, an occasional patch broke away from the coherent ribbon above the water and drifted slowly among the sweetgum and magnolia trees that... trees left for shade when the virgin floodplain forest had been cleared. Owls came to roost and hawks took up their vigil. Rodents and rabbits emerged...Small Mississippian Community Christopher S. Peebles .................... 394 Vi i 0% . i • • • • • • • . • • • • N L 4 _ through counting tree rings

Evolution of the Proximal Sealing Rings of the Anaconda Stent-Graft After Endovascular Aneurysm Repair.

PubMed

Koenrades, Maaike A; Klein, Almar; Leferink, Anne M; Slump, Cornelis H; Geelkerken, Robert H

2018-04-01

To provide insight into the evolution of the saddle-shaped proximal sealing rings of the Anaconda stent-graft after endovascular aneurysm repair (EVAR). Eighteen abdominal aortic aneurysm patients were consecutively enrolled in a single-center, prospective, observational cohort study (LSPEAS; Trialregister.nl identifier NTR4276). The patients were treated electively using an Anaconda stent-graft with a mean 31% oversizing (range 17-47). According to protocol, participants were to be followed for 2 years, during which 5 noncontrast electrocardiogram-gated computed tomography scans would be conducted. Three patients were eliminated within 30 days (1 withdrew, 1 died, and a third was converted before stent-graft deployment), leaving 15 patients (mean age 72.8±3.7 years; 14 men) for this analysis. Evolution in size and shape (symmetry) of both proximal infrarenal sealing rings were assessed from discharge to 24 months using dedicated postprocessing algorithms. At 24 months, the mean diameters of the first and second ring stents had increased significantly (first ring: 2.2±1.0 mm, p<0.001; second ring: 2.7±1.1 mm, p<0.001). At 6 months, the first and second rings had expanded to a mean 96.6%±2.1% and 94.8%±2.7%, respectively, of their nominal diameter, after which the rings expanded slowly; ring diameters stabilized to near nominal size (first ring, 98.3%±1.1%; second ring, 97.2%±1.4%) at 24 months irrespective of initial oversizing. No type I or III endoleaks or aneurysm-, device-, or procedure-related adverse events were noted in follow-up. The difference in the diametric distances between the peaks and valleys of the saddle-shaped rings was marked at discharge but became smaller after 24 months for both rings (first ring: median 2.0 vs 1.2 mm, p=0.191; second ring: median 2.8 vs 0.8 mm; p=0.013). Irrespective of initial oversizing, the Anaconda proximal sealing rings radially expanded to near nominal size within 6 months after EVAR. Initial oval-shaped rings conformed symmetrically and became nearly circular through 24 months. These findings should be taken into account in planning and follow-up.

Vasodilatory effects of ethanol extract of Radix Paeoniae Rubra and its mechanism of action in the rat aorta.

PubMed

Jin, Song Nan; Wen, Jin Fu; Wang, Ting Ting; Kang, Dae Gill; Lee, Ho Sub; Cho, Kyung Woo

2012-06-26

Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined. The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings. Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta. EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with N(G)-nitro-L-arginine methylester (L-NAME) or 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ). Extracellular Ca²⁺ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca²⁺ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd³⁺, and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective K(Ca) channels blocker, or glibenclamide, an ATP-sensitive K⁺ channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation. The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both K(Ca) and K(ATP) channels and inhibition of L-type Ca²⁺ channels. Copyright © 2012. Published by Elsevier Ireland Ltd.

[Late outlet strut fracture of an aortic Björk-Shiley and embolization of the prosthetic disc].

PubMed

Brochet, E; Bougis de Brux, M A; Assayag, P; Benacin, Y; Gamerman, G; Guerot, C; Valère, P E

1988-09-01

A new case of late fracture of an outlet strut in a convexo-concave Björk-Shiley valve is reported. The fracture occurred 6 years after aortic implantation of the valve and was responsible for aorto-iliac embolization by the prosthetic disc and death of the patient from cardiogenic shock. This not uncommon complication of the Björk-Shiley valve prosthesis is usually ascribed to the relative fragility of its outlet strut welded to the metallic ring and subjected to strong pressures. Although most cases were observed within the first two years of prosthetic valve insertion, and mainly with valves manufactured in 1981 and 1982, our case and a few others demonstrate the possibility of late rupture. Cardiologists must be aware of this possible complication, since in some favourable cases it can be diagnosed at an early stage and the patient's life can be saved by an emergency operation.

Aortic reactivity and electrophysiology in normotensive rats, spontaneously hypertensive rats and rats made hypertensive with desoxycorticosterone plus salt

PubMed Central

Massingham, R.; Shevde, S.

1971-01-01

The mechanical and electrophysiological activity of rings and strips of thoracic aortic smooth muscle taken from normotensive, DOCA-hypertensive and New Zealand spontaneously hypertensive (A.S. strain) rats have been compared. Aortae from A.S.-hypertensive rats developed less tension in the presence of noradrenaline and K+ than those isolated from normotensive and DOCA-hypertensive rats. Aortae from DOCA-hypertensive rats developed the same tension in response to K+ as normotensive rats but were less reactive to noradrenaline. Measurements of resting membrane potentials from the three groups of rats demonstrated that whereas normotensive and DOCA-hypertensive rats had similar resting membrane potentials, those from A.S.-hypertensive rats were significantly lower (P<0.001). It is suggested that the enhanced responsiveness of intact vascular beds in A.S.-hypertensive rats is a consequence of a change in the geometry of the blood vessels rather than an increase in the contractor response of the smooth muscle cells. PMID:5152033

Effects of Hindlimb Unweighting on Arterial Contractile Responses in Mice

NASA Technical Reports Server (NTRS)

Ma, Jia; Ren, Xin-Ling; Purdy, Ralph E.

2003-01-01

The aim of this work was to determine if hindlimb unweighting in mice alters arterial contractile responses. Sixteen male C57B/6 mice and 16 male Chinese Kunming mice were divided into control and 3 weeks hindlimb unweighting groups, respectively. Using isolated arterial rings from different arteries of mouse, effects of 3 weeks hindlimb unweighting on arterial contractile responsiveness were examined in vitro. The results showed that, in arterial rings from both C57B/6 and Chinese Kunming mice, maximum isometric contractile tensions evoked by either KCl or phenylephrine were significantly lower in abdominal aortic, mesenteric arterial and femoral arterial rings from hindlimb unweighting, compared to control mice. However, the maximal contractile responses of common carotid rings to KCl and PE were not significantly different between control and hindlimb unweighting groups. The sensitivity (EC(sub 50)) of all arteries to KCl or PE showed no significant differences between control and hindlimb unweighting mice. These data indicated that 3 weeks hindlimb unweighting results in a reduced capacity of the arterial smooth muscle of the hindquarter to develop tension. In addition, the alterations in arterial contractile responses caused by hindlimb unweighting in mice are similar as those in rats. Our work suggested that hindlimb unweighting mouse model may be used as a model for the study of postflight cardiovascular deconditioning.

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats.

PubMed

Liang, Zhengyang; Zheng, Yuanyuan; Wang, Jing; Zhang, Quanbin; Ren, Shuang; Liu, Tiantian; Wang, Zhiqiang; Luo, Dali

2016-09-15

Low molecular weight fucoidan (LMWF) was prepared from Laminaria japonica Areschoug, a popular seafood and medicinal plant consumed in Asia. Chinese have long been using it as a traditional medicine for curing hypertension and edema. This study was intent to investigate the possible beneficial effect of LMWF on hyper-responsiveness of aortic smooth muscles instreptozotocin (STZ)-induced type 1 diabetic rats. Sprague-Dawley rats were made diabetic by injection of STZ, followed by the administration of LMWF (50 or 100mg/kg/day) or probucol (100mg/kg/day) for 12 weeks. Body weight, blood glucose level, basal blood pressure, serum lipid profiles, oxidative stress, prostanoids production, and vasoconstriction response of endothelium-denuded aorta rings to phenylephrine were measured by Real time-PCR, Western blots, ELISA assay, and force myograph, respectively. LMWF (100mg/kg/day)-treated group showed robust improvements on STZ-induced body weight-loss, hypertension, and hyperlipidaemia as indicated by decreased serum level of total cholesterol, triglyceride, and low density lipoprotein cholesterol; while probucol, a lipid-modifying drug with antioxidant properties, displayed mild effects. In addition, LMWF appreciably ameliorated STZ-elicited hyper-responsiveness and oxidative stress in aortic smooth muscles as indicated by decreased superoxide level, increased glutathione content and higher superoxide dismutase activity. Furthermore, administration with LMWF dramatically prevented cyclooxygenase-2 stimulation and restored the up-regulation of thromboxane synthase and down-regulation of 6-keto-PGF1α (a stable metabolic product of prostaglandin I2) in the STZ-administered rats. This study demonstrates for the first time that LMWF can protect against hyperlipidaemia, hypertension, and hyper-responsiveness of aortic smooth muscles in type 1 diabetic rat via, at least in part, amelioration of oxidative stress and restoration of prostanoids levels in aortic smooth muscles. Therefore, LMWF can be a potential adjuvant treatment against cardiovascular complications in type 1 diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

PubMed Central

Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A.; Meseguer-Olmo, Luis; De Aza, Piedad N.

2016-01-01

This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released. PMID:28773906

Successful implantation of physiologically functional bioengineered mouse internal anal sphincter.

PubMed

Raghavan, Shreya; Miyasaka, Eiichi A; Hashish, Mohamed; Somara, Sita; Gilmont, Robert R; Teitelbaum, Daniel H; Bitar, Khalil N

2010-08-01

We have previously developed bioengineered three-dimensional internal anal sphincter (IAS) rings from circular smooth muscle cells isolated from rabbit and human IAS. We provide proof of concept that bioengineered mouse IAS rings are neovascularized upon implantation into mice of the same strain and maintain concentric smooth muscle alignment, phenotype, and IAS functionality. Rings were bioengineered by using smooth muscle cells from the IAS of C57BL/6J mice. Bioengineered mouse IAS rings were implanted subcutaneously on the dorsum of C57BL/6J mice along with a microosmotic pump delivering fibroblast growth factor-2. The mice remained healthy during the period of implantation, showing no external signs of rejection. Mice were killed 28 days postsurgery and implanted IAS rings were harvested. IAS rings showed muscle attachment, neovascularization, healthy color, and no external signs of infection or inflammation. Assessment of force generation on harvested IAS rings showed the following: 1) spontaneous basal tone was generated in the absence of external stimulation; 2) basal tone was relaxed by vasoactive intestinal peptide, nitric oxide donor, and nifedipine; 3) acetylcholine and phorbol dibutyrate elicited rapid-rising, dose-dependent, sustained contractions repeatedly over 30 min without signs of muscle fatigue; and 4) magnitudes of potassium chloride-induced contractions were 100% of peak maximal agonist-induced contractions. Our preliminary results confirm the proof of concept that bioengineered rings are neovascularized upon implantation. Harvested rings maintain smooth muscle alignment and phenotype. Our physiological studies confirm that implanted rings maintain 1) overall IAS physiology and develop basal tone, 2) integrity of membrane ionic characteristics, and 3) integrity of membrane associated intracellular signaling transduction pathways for contraction and relaxation by responding to cholinergic, nitrergic, and VIP-ergic stimulation. IAS smooth muscle tissue could thus be bioengineered for the purpose of implantation to serve as a potential graft therapy for dysfunctional internal anal sphincter in fecal incontinence.

Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles.

PubMed

Zhang, Jun; Wang, Jin-Liang; Yu, Wei-Fa; Zhou, Zhi-Ming; Tao, Wen-Chang; Wang, Yi-Cheng; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

2013-11-01

Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT₁ receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT₁ receptor binding affinity and high AT₁ receptor selectivity over AT₂ receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT₁ IC₅₀ = 3 nM, AT₂ IC₅₀ > 10,000 nM, PA₂ = 8.51) and 11g (AT₁ IC₅₀ = 0.1 nM, AT₂ IC₅₀ = 149 nM, PA₂ = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT₁ receptor antagonists in spontaneous hypertensive rats. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Comparison of Six Generic Vancomycin Products for Treatment of Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis in Rabbits

PubMed Central

Tattevin, P.; Saleh-Mghir, A.; Davido, B.; Ghout, I.; Massias, L.; Garcia de la Maria, C.; Miró, J. M.; Perronne, C.; Laurent, F.

2013-01-01

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 107 CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 μg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 μg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) μg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America. PMID:23254435

Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046).

PubMed

Hiraku, S; Taniguchi, K; Wakitani, K; Omawari, N; Kira, H; Miyamoto, T; Okegawa, T; Kawasaki, A; Ujiie, A

1986-07-01

The effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046) on thromboxane A2 (TXA2) synthetase in vitro and on experimental animal models of sudden death and cerebral infarction were studied. IC50 values of OKY-046 for the TXA2 synthetase of human, rabbit, dog and guinea pig washed platelets were 0.004, 0.004, 0.26 and 2.4 microM, respectively. OKY-046 at concentrations up to 1 mM, however, did not inhibit prostacyclin (PGI2) synthetase from bovine aorta microsomes or cyclooxygenase and PGE2 isomerase from sheep seminal vesicle microsomes. Similarly, platelet 12-lipoxygenase was not affected by OKY-046. Evidence for a re-direction of arachidonate metabolism from thromboxane synthesis toward PGI2 synthesis was obtained using rat peritoneal cells. Namely, OKY-046 increased PGI2 production accompanied by an inhibition of TXA2 production at a concentration of more than 1 microM. OKY-046 at a dose of 0.1 mg/kg (i.v.) in dogs inhibited the aortic and mesenteric arterial contraction of rabbit induced by the addition of arachidonate to extracorporated blood of the dogs. OKY-046 at a dose of 0.3 mg/kg (i.v.) prevented the arachidonate-induced sudden death and also decreased the incidence of cerebral infarction induced by injection of arachidonate into the internal carotid artery in rabbits. Aspirin also decreased the incidence of cerebral infarction at a dose of 30 mg/kg (i.v.). These results suggest that OKY-046 may be valuable for the treatment of cerebrovascular and cardiovascular diseases associated with vasoconstriction and thrombosis due to TXA2.

Elective tracheostomy in intensive care unit: Looking between techniques, a three cases report

PubMed Central

Ferraro, Fausto; Marullo, Lucia; d’Elia, Anna; Izzo, Giuseppe

2014-01-01

There is no optimal tracheostomy (TS) technique, proved to be the best. For this reason, operators’ skills, clinical anatomical and physio-pathological features of the patient should be considered as discriminating factors in the choice of percutaneous dilation tracheostomy (PDT) technique. This article includes reports of three cases of PDT: In the first case distance between jugular notch and the first tracheal ring was too long, the second case involving a patient with mild ectasia of the ascending aorta and aortic regurgitation with De Musset's sign with great risk of perioperative bleeding and a third case, of tracheomalacia with inflammatory stenosis at the 4th tracheal ring. All together, this case series describes how decisions were made by an experienced staff, in which the patient characteristics were assessed and techniques best suited for each case were implemented. PMID:24963186

Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

PubMed Central

Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

2014-01-01

Objectives This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). Methods The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Results Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Conclusions Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. PMID:24533142

Mechanism of vasorelaxation induced by Tridax procumbens extract in rat thoracic aorta

PubMed Central

Salahdeen, Hussein Mofomosara; Idowu, Gbolahan O; Salami, Shakiru A; Murtala, Babatunde A; Alada, AbdulRasak A

2016-01-01

Background/Aim: Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). Materials and Methods: The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10–7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. Results: The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. Conclusion: These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP. PMID:27104039

Mechanism of vasorelaxation induced by Tridax procumbens extract in rat thoracic aorta.

PubMed

Salahdeen, Hussein Mofomosara; Idowu, Gbolahan O; Salami, Shakiru A; Murtala, Babatunde A; Alada, AbdulRasak A

2016-01-01

Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10-7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP.

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

PubMed

Rattmann, Yanna D; Crestani, Sandra; Lapa, Fernanda R; Miguel, Obdúlio G; Marques, Maria C A; da Silva-Santos, J Eduardo; Santos, Adair R S

2009-01-01

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

Phosphate binding reduces aortic angiotensin-converting enzyme and enhances nitric oxide bioactivity in experimental renal insufficiency.

PubMed

Eräranta, Arttu; Törmänen, Suvi; Kööbi, Peeter; Vehmas, Tuija I; Lakkisto, Päivi; Tikkanen, Ilkka; Moilanen, Eeva; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka

2014-01-01

Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking. Fifteen weeks after 5/6 nephrectomy (NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham). Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups. Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.

HZE ⁵⁶Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase.

PubMed

Soucy, Kevin G; Lim, Hyun Kyo; Kim, Jae Hyung; Oh, Young; Attarzadeh, David O; Sevinc, Baris; Kuo, Maggie M; Shoukas, Artin A; Vazquez, Marcelo E; Berkowitz, Dan E

2011-10-01

Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.

Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

PubMed Central

Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

2016-01-01

Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol.

PubMed

do Vale, Gabriel T; Simplicio, Janaina A; Gonzaga, Natália A; Yokota, Rodrigo; Ribeiro, Amanda A; Casarini, Dulce E; de Martinis, Bruno S; Tirapelli, Carlos R

2018-04-30

Chronic ethanol consumption is associated with hypertension and atherosclerosis. Vascular oxidative stress is described as an important mechanism whereby ethanol predisposes to atherosclerosis. We hypothesized that nebivolol would prevent ethanol-induced hypertension and vascular oxidative stress. Male Wistar rats were treated with ethanol 20% (vol./vol.) or nebivolol (10 mg/kg/day, p. o., gavage), a selective β 1 -adrenergic receptor antagonist. Ethanol-induced increase in blood pressure and in the circulating levels of adrenaline and noradrenaline was prevented by nebivolol. Similarly, nebivolol prevented ethanol-induced increase in plasma levels of renin, angiotensin I and II. Chronic ethanol consumption increased the aortic levels of superoxide anion (O 2 - ), thiobarbituric acid reactive species (TBARS) as well as the expression of Nox1 and nitrotyrosine immunostaining in the rat aorta. Treatment with nebivolol prevented these responses. The decrease in aortic levels of nitrate/nitrite (NOx) induced by ethanol was prevented by the treatment with nebivolol. Finally, nebivolol attenuated ethanol-induced increase in phenylephrine- and noradrenaline-induced contraction of endothelium-intact and endothelium-denuded aortic rings. The novelty of our study is that nebivolol prevented ethanol-induced hypertension and vascular oxidative stress. Additionally, we showed that the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) are important endogenous mediators of the cardiovascular effects of ethanol. Copyright © 2018 Elsevier B.V. All rights reserved.

Hyperphosphatemia induces cellular senescence in human aorta smooth muscle cells through integrin linked kinase (ILK) up-regulation.

PubMed

Troyano, Nuria; Nogal, María Del; Mora, Inés; Diaz-Naves, Manuel; Lopez-Carrillo, Natalia; Sosa, Patricia; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruiz-Torres, María P

2015-12-01

Aging is conditioned by genetic and environmental factors. Hyperphosphatemia is related to some pathologies, affecting to vascular cells behavior. This work analyze whether high concentration of extracellular phosphate induces vascular smooth muscle cells senescence, exploring the intracellular mechanisms and highlighting the in vivo relevance of this phenomenon. Human aortic smooth muscle cells treated with β-Glycerophosphate (BGP, 10mM) suffered cellular senescence by increasing p53, p21 and p16 expression and the senescence associated β-galactosidase activity. In parallel, BGP induced ILK overexpression, dependent on the IGF-1 receptor activation, and oxidative stress. Down-regulating ILK expression prevented BGP-induced senescence and oxidative stress. Aortic rings from young rats treated with 10mM BGP for 48h, showed increased p53, p16 and ILK expression and SA-β-gal activity. Seven/eight nephrectomized rats feeding a hyperphosphatemic diet and fifteenth- month old mice showed hyperphosphatemia and aortic ILK, p53 and p16 expression. In conclusion, we demonstrated that high extracellular concentration of phosphate induced senescence in cultured smooth muscle through the activation of IGF-1 receptor and ILK overexpression and provided solid evidences for the in vivo relevance of these results since aged animals showed high levels of serum phosphate linked to increased expression of ILK and senescence genes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endoplasmic reticulum stress in perivascular adipose tissue promotes destabilization of atherosclerotic plaque by regulating GM-CSF paracrine.

PubMed

Ying, Ru; Li, Sheng-Wei; Chen, Jia-Yuan; Zhang, Hai-Feng; Yang, Ying; Gu, Zhen-Jie; Chen, Yang-Xin; Wang, Jing-Feng

2018-04-18

Perivascular adipose tissue (PVAT) accelerates plaque progression and increases cardiovascular risk. We tested the hypothesis that PVAT contributed to plaque vulnerability and investigated whether endoplasmic reticulum stress (ER stress) in PVAT played an important role in vulnerable plaque. We transplanted thoracic aortic PVAT or subcutaneous adipose tissue as a control, from donor mice to carotid arteries of recipient apolipoprotein E deficient (apoE -/- ) mice after removing carotid artery collar placed for 6 weeks. Two weeks after transplantation, ER stress inhibitor 4-phenyl butyric acid (4-PBA) was locally administrated to the transplanted PVAT and then animals were euthanized after 4 weeks. Immunohistochemistry was performed to quantify plaque composition and neovascularization. Mouse angiogenesis antibody array kit was used to test the angiogenic factors produced by transplanted adipose tissue. In vitro tube formation assay, scratch wound migration assay and mouse aortic ring assay were used to assess the angiogenic capacity of supernatant of transplanted PVAT. Ultrastructural detection by transmission electron microscopy showed transplanted PVAT was a mixed population of white and brown adipocytes with abundant mitochondria. Transplanted PVAT increased the intraplaque macrophage infiltration, lipid core, intimal and vasa vasorum neovascularization and MMP2/9 expression in plaque while decreased smooth muscle cells and collagen in atherosclerotic plaque, which were restored by local 4-PBA-treatment. Antibody array analysis showed that 4-PBA reduced several angiogenic factors [Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), MCP-1, IL-6] secreted by PVAT. Besides, conditioned medium from 4-PBA treated-PVAT inhibited tube formation and migration capacity of endothelial cells and ex vivo mouse aortic ring angiogenesis compared to conditioned medium from transplanted PVAT. mRNA expression and protein levels of GM-CSF were markedly elevated in adipocytes under ER stress which would be suppressed by 4-PBA. In addition, ER stress enhanced NF-κB binding to the promoter of the mouse GM-CSF gene in adipocytes confirmed by Chromatin immunoprecipitation analyses. Our findings demonstrate that ER stress in PVAT destabilizes atherosclerotic plaque, in part through increasing GM-CSF paracrine via transcription factor NF-κB.

Acyl Chain-Dependent Effect of Lysophosphatidylcholine on Endothelium-Dependent Vasorelaxation

PubMed Central

Rao, Shailaja P.; Riederer, Monika; Lechleitner, Margarete; Hermansson, Martin; Desoye, Gernot; Hallström, Seth; Graier, Wolfgang F.; Frank, Saša

2013-01-01

Previously we identified palmitoyl-, oleoyl-, linoleoyl-, and arachidonoyl-lysophosphatidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the impact of those LPC on acetylcholine (ACh)- induced vascular relaxation. All tested LPC attenuated ACh-induced relaxation, measured ex vivo, using mouse aortic rings and wire myography. The rank order of potency was as follows: 18:2>20:4>16:0>18:1. The attenuating effect of LPC 16:0 on relaxation was augmented by indomethacin-mediated cyclooxygenase (COX)-inhibition and CAY10441, a prostacyclin (PGI2)- receptor (IP) antagonist. Relaxation attenuated by LPC 20:4 and 18:2 was improved by indomethacin and SQ29548, a thromboxane A2 (TXA2)- receptor antagonist. The effect of LPC 20:4 could also be improved by TXA2- and PGI2-synthase inhibitors. As determined by EIA assays, the tested LPC promoted secretion of PGI2, TXA2, PGF2α, and PGE2, however, with markedly different potencies. LPC 16:0 was the most potent inducer of superoxide anion production by mouse aortic rings, followed by LPC 18:2, 20:4 and 18:1, respectively. The strong antioxidant tempol recovered relaxation impairment caused by LPC 18:2, 18:1 and 20:4, but not by LPC 16:0. The tested LPC attenuate ACh-induced relaxation through induction of proconstricting prostanoids and superoxide anions. The potency of attenuating relaxation and the relative contribution of underlying mechanisms are strongly related to LPC acyl-chain length and degree of saturation. PMID:23741477

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through nitric oxide and Akt.

PubMed

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2011-04-01

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous nitric oxide (NO) synthase (NOS) inhibitors asymmetrical dimethylarginine (ADMA) and L-NG-monomethyl arginine (L-NMMA). This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA-independent effects that influence endothelial function. Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in human umbilical vein endothelial cells, we found that DDAH1 acts to promote endothelial cell proliferation, migration, and tube formation by Akt phosphorylation, as well as through the traditional role of degrading ADMA. Incubation of human umbilical vein endothelial cells with the NOS inhibitors l-NG-nitro-arginine methyl ester (L-NAME) or ADMA, the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-2)quinoxalin-1-one, or the cGMP analog 8-(4-Chlorophenylthio)-cGMP had no effect on phosphorylated (p)-Akt(Ser473), indicating that the increase in p-Akt(Ser473) produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase in p-Akt(Ser473). Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. DDAH1 exerts a unique role in activating Akt that affects endothelial function independently of degrading endogenous NOS inhibitors.

JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.

PubMed

Kiziltepe, Tanyel; Anderson, Kenneth C; Kutok, Jeffery L; Jia, Lee; Boucher, Kenneth M; Saavedra, Joseph E; Keefer, Larry K; Shami, Paul J

2010-01-01

Glutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O(2)-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity. We studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice. JS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 microm at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 microm, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 microm. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 microm JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. JS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment.

Inhibition of angiogenesis: a novel antitumor mechanism of the herbal compound arctigenin.

PubMed

Gu, Yuan; Scheuer, Claudia; Feng, Dilu; Menger, Michael D; Laschke, Matthias W

2013-09-01

Arctigenin, a functional ingredient of several traditional Chinese herbs, has been reported to have potential antitumor activity. However, its mechanisms of action are still not well elucidated. Because the establishment and metastatic spread of tumors is crucially dependent on angiogenesis, here we investigated whether arctigenin inhibits tumor growth by disturbing blood vessel formation. For this purpose, human dermal microvascular endothelial cells were exposed to different arctigenin doses to study their viability, proliferation, protein expression, migration, and tube formation compared with vehicle-treated controls. In addition, arctigenin action on vascular sprouting was analyzed in an aortic ring assay. Furthermore, we studied direct arctigenin effects on CT26.WT colon carcinoma cells. Spheroids of these tumor cells were transplanted into the dorsal skinfold chamber of arctigenin-treated and vehicle-treated BALB/c mice for the in-vivo analysis of tumor vascularization and growth by intravital fluorescence microscopy, histology, and immunohistochemistry. We found that noncytotoxic doses of arctigenin dose dependently reduced the proliferation of human dermal microvascular endothelial cells without affecting their migratory and tube-forming capacity. Arctigenin treatment also resulted in a decreased cellular expression of phosphorylated serine/threonine protein kinase AKT, vascular endothelial growth factor receptor 2, and proliferating cell nuclear antigen and inhibited vascular sprouting from aortic rings. In addition, proliferation, but not secretion of vascular endothelial growth factor, was decreased in arctigenin-treated tumor cells. Finally, arctigenin suppressed the vascularization and growth of engrafting CT26.WT tumors in the dorsal skinfold chamber model. Taken together, these results show for the first time an antiangiogenic action of arctigenin, which may contribute considerably toward its antitumor activity.

Noncontact optical measurement of lens capsule thickness ex vivo

NASA Astrophysics Data System (ADS)

Ziebarth, Noel M.; Manns, Fabrice; Uhlhorn, Stephen; Parel, Jean-Marie

2004-07-01

Purpose: To design a non-contact optical system to measure lens capsule thickness in cadaver eyes. Methods: The optical system uses a 670nm laser beam delivered to a single-mode fiber coupler. The output of the fiber coupler is focused onto the tissue using an aspheric lens (NA=0.68) mounted on a motorized translation stage. Light reflected from the sample is collected by the fiber coupler and sent to a silicon photodiode connected to a power meter. Peaks in the power signal are detected when the focal point of the aspheric lens coincides with the capsule boundaries. The capsule thickness is proportional to the distance between successive peaks. Anterior and posterior lens capsule thickness measurements were performed on 13 human, 10 monkey, and 34 New Zealand white rabbit lenses. The cadaver eyes were prepared for optical measurements by bonding a PMMA ring on the sclera. The posterior pole was sectioned, excess vitreous was removed, and the eye was placed on a Teflon slide. The cornea and iris were then sectioned. After the experiments, the lenses were excised, placed in 10% buffered formalin, and prepared for histology. Results: Central anterior lens capsule thickness was 9.4+/-2.9μm (human), 11.2+/-6.6μm (monkey), and 10.3+/-3.6μm (rabbit) optically and 14.9+/-1.6μm (human), 17.7+/-4.9μm (monkey), and 12.6+/-2.3μm (rabbit) histologically. The values for the central posterior capsule were 9.4+/-2.9μm (human), 6.6+/-2.5μm (monkey), and 7.9+/-2.3μm (rabbit) optically and 4.6+/-1.4μm (human), 4.5+/-1.2μm (monkey), and 5.7+/-1.7μm (rabbit) histologically. Conclusions: This study demonstrates that a non-contact optical system can successfully measure lens capsule thickness in cadaver eyes.

Effects of positive acceleration on the metabolism of endogenous carbon monoxide and serum lipid in atherosclerotic rabbits

PubMed Central

Luo, Huilan; Chen, Yongsheng; Wang, Junhua

2010-01-01

Background: Atherosclerosis (AS) is caused mainly due to the increase in the serum lipid, thrombosis, and injuries of the endothelial cells. During aviation, the incremental load of positive acceleration that leads to dramatic stress reactions and hemodynamic changes may predispose pilots to functional disorders and even pathological changes of organs. However, much less is known on the correlation between aviation and AS pathogenesis. Methods and Results: A total of 32 rabbits were randomly divided into 4 groups with 8 rabbits in each group. The control group was given a high cholesterol diet but no acceleration exposure, whereas the other 3 experimental groups were treated with a high cholesterol diet and acceleration exposure for 4, 8, and 12 weeks, respectively. In each group, samples of celiac vein blood and the aorta were collected after the last exposure for the measurement of endogenous CO and HO-1 activities, as well as the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). As compared with the control group, the endocardial CO content and the HO-1 activity in aortic endothelial cells were significantly elevated at the 4th, 8th, and 12th weekend, respectively (P < 0.05 or <0.01). And these measures tended upward as the exposure time was prolonged. Levels of TC and LDL-C in the experimental groups were significantly higher than those in the control group, presenting an upward tendency. Levels of TG were found significantly increased in the 8-week-exposure group, but significantly declined in the 12-week-exposure group (still higher than those in the control group). Levels of the HDL-C were increased in the 4-week-exposure group, declined in the 8-week-exposure group, and once more increased in the 12-week-exposure group, without significant differences with the control group. Conclusions: Positive acceleration exposure may lead to a significant increase of endogenous CO content and HO-1 activity and a metabolic disorder of serum lipid in high-cholesterol diet–fed rabbits, which implicates that the acceleration exposure might accelerate the progression of AS. PMID:20877690

The spinal cord dura mater reaction to nitinol and titanium alloy particles: a 1-year study in rabbits

PubMed Central

Rhalmi, Souad; Charette, Sylvie; Assad, Michel; Coillard, Christine

2007-01-01

This investigation was undertaken to simulate in an animal model the particles released from a porous nitinol interbody fusion device and to evaluate its consequences on the dura mater, spinal cord and nerve roots, lymph nodes (abdominal para-aortic), and organs (kidneys, spleen, pancreas, liver, and lungs). Our objective was to evaluate the compatibility of the nitinol particles with the dura mater in comparison with titanium alloy. In spite of the great use of metallic devices in spine surgery, the proximity of the spinal cord to the devices raised concerns about the effect of the metal debris that might be released onto the neural tissue. Forty-five New Zealand white female rabbits were divided into three groups: nitinol (treated: N = 4 per implantation period), titanium (treated: N = 4 per implantation period), and sham rabbits (control: N = 1 per observation period). The nitinol and titanium alloy particles were implanted in the spinal canal on the dura mater at the lumbar level L2–L3. The rabbits were sacrificed at 1, 4, 12, 26, and 52 weeks. Histologic sections from the regional lymph nodes, organs, from remote and implantation sites, were analyzed for any abnormalities and inflammation. Regardless of the implantation time, both nitinol and titanium particles remained at the implantation site and clung to the spinal cord lining soft tissue of the dura mater. The inflammation was limited to the epidural space around the particles and then reduced from acute to mild chronic during the follow-up. The dura mater, sub-dural space, nerve roots, and the spinal cord were free of reaction. No particles or abnormalities were found either in the lymph nodes or in the organs. In contact with the dura, the nitinol elicits an inflammatory response similar to that of titanium. The tolerance of nitinol by a sensitive tissue such as the dura mater during the span of 1 year of implantation demonstrated the safety of nitinol and its potential use as an intervertebral fusion device. PMID:17334794

Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

PubMed

Pieper, G M; Siebeneich, W

1998-07-01

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

Dynamic contrast-enhanced x-ray CT measurement of cerebral blood volume in a rabbit tumor model

NASA Astrophysics Data System (ADS)

Cenic, Aleksa; Lee, Ting-Yim; Craen, Rosemary A.; Gelb, Adrian W.

1998-07-01

Cerebral blood volume (CBV) is a major determinant of intracranial pressure (ICP). Hyperventilation is commonly employed to reduce raised ICP (e.g. in brain tumour patients) presumably through its effect on CBV. With the advent of slip- ring CT scanners, dynamic contrast-enhanced imaging allows for the measurement of CBV with high spatial resolution. Using a two-compartment model to characterize the distribution of X- ray contrast agent in the brain, we have developed a non- equilibrium CT method to measure CBV in normal and pathological regions. We used our method to investigate the effect of hyperventilation on CBV during propofol anaesthesia in rabbits with implanted brain tumours. Eight New Zealand White rabbits with implanted VX2 carcinoma brain tumours were studied. For each rabbit, regional CBV measurements were initially made at normocapnia (PaCO2 40 mmHg) and then at hyperventilation (PaCO2 25 mmHg) during propofol anaesthesia. The head was positioned such that a coronal image through the brain incorporated a significant cross-section of the brain tumour as well as a radial artery in a forelimb. Images at the rate of 1 per second were acquired for 2 minutes as Omnipaque 300 (1.5 ml/kg rabbit weight) was injected via a peripheral vein. In these CT images, regions of interest in the brain tissue (e.g. tumour, contra-lateral normal, and peri-tumoural) and the radial artery were drawn. For each region, the mean CT number in pre-contrast images was subtracted from the mean CT number in post-contrast images to produce either the tissue contrast concentration curve, or the arterial contrast concentration curve. Using our non- equilibrium analysis method based on a two-compartment model, regional CBV values were determined from the measured contrast concentration curves. From our study, the mean CBV values [+/- SD] in the tumour, peri-tumoural, and contra-lateral normal regions during normocapnia were: 5.47 plus or minus 1.97, 3.28 plus or minus 1.01, and 1.86 plus or minus 0.54 ml/100 g, respectively. Following hyperventilation, we found a significant decrease (p less than 0.025) of 10.4% in CBV in the peri-tumoural region, and no statistically significant change in CBV in the tumour or contra-lateral normal regions. We have developed a convenient method for measuring CBV in normal and pathological tissue using a slip-ring CT scanner. In a brain tumour model, we found that CBV was markedly increased in tumour and peri-tumoural regions compared to normal regions. Our results suggest that the reduction of raised ICP following hyperventilation during propofol anaesthesia may be mainly due to a reduction in CBV in the peri-tumoural tissue rather than in the bulk of the tumour or normal regions. Our method has the potential to provide further knowledge on the cerebral hemodynamics of space- occupying lesions during different anaesthetic interventions or treatment regiments.

Antioxidative and Cholesterol-Lowering Effects of Lemon Essential Oil in Hypercholesterolemia-Induced Rabbits

PubMed Central

Lee, Hyunjoo; Woo, Minji; Kim, Mijeong; Noh, Jeong Sook

2018-01-01

The cholesterol-lowering and anti-atherogenic effects of lemon essential oil (LEO) were investigated and compared with the effects of limonene. Owing to their volatility, both LEO and limonene were microencapsulated before preparation of the diet (20%, w/w). Hypercholesterolemia-induced rabbits were divided into 3 groups based on plasma total cholesterol (TC) levels and fed coating matrix (control group), LEO (LEO group), or limonene (Limonene group) for 8 weeks. LEO dose-dependently inhibited low-density lipoprotein oxidation in vitro. Plasma TC levels were the lowest in the LEO group (P<0.05). Erythrocytes in the LEO group had a normal disc shape, whereas the erythrocytes in the limonene and control groups were aggregated and star-shaped, respectively. The aortic intima thickness was thinnest in the LEO group followed by the control and limonene groups. Plasma TC lowering and anti-atherogenic effects of LEO were greater than limonene, suggesting that other bioactive compounds besides limonene in LEO might contribute to these effects. The bioactive compounds in LEO were limonene (67.57%), β-pinene (10.00%), and γ-terpinene (9.95%). In addition, sabinene, α-pinene, myrcene, and geranial were also present but the amount was in the range of 1~2%. Several bioactive compounds were also detected. In conclusion, LEO had beneficial effects on hypercholesterolemia due to its antioxidative and cholesterol lowering effects. PMID:29662842

Acidic fibroblast growth factor (FGF) but not basic FGF induces sleep and fever in rabbits.

PubMed

Knefati, M; Somogyi, C; Kapás, L; Bourcier, T; Krueger, J M

1995-07-01

Acidic fibroblast growth factor (FGF) and basic FGF belong to a growth factor family. Interleukin-1, another member of that family, is involved in sleep regulation. FGFs and interleukin-1 share structural and functional features. We therefore determined whether acidic FGF and basic FGF were somnogenic. Male New Zealand White rabbits were provided with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular (icv) cannula. The animals were injected icv with isotonic NaCl (control) and on separate days with one of three doses of acidic or basic FGF (0.01, 0.1, or 1.0 micrograms) or with heat-treated acidic FGF (1.0 micrograms). The EEG, brain temperature, and motor activity were recorded for 23 h. The biological activity of basic FGF was determined in vitro by its ability to induce DNA synthesis in rat aortic smooth muscle cells. Acidic FGF induced prolonged dose-related increases in non-rapid eye movement sleep beginning in the 1st postinjection h and continuing for 12-23 h after the treatment. Acidic FGF also induced fevers of approximately 1 degree C after the 1.0 micrograms dose. Both activities of acidic FGF were lost after heat treatment. In contrast, basic FGF lacked somnogenic and pyrogenic activity, although it did induce DNA synthesis. Current results suggest that acidic FGF is part of the complex cytokine network in brain involved in sleep regulation.

Specificity of the Antibody Receptor Site to D-Lysergamide: Model of a Physiological Receptor for Lysergic Acid Diethylamide

PubMed Central

Vunakis, Helen Van; Farrow, John T.; Gjika, Hilda B.; Levine, Lawrence

1971-01-01

Antibodies to D-lysergic acid have been produced in rabbits and guinea pigs and a radioimmunoassay for the hapten was developed. The specificity of this lysergamide-antilysergamide reaction was determined by competitive binding with unlabeled lysergic acid diethylamide (LSD), psychotomimetic drugs, neurotransmitters, and other compounds with diverse structures. LSD and several related ergot alkaloids were potent competitors, three to seven times more potent than lysergic acid itself. The N,N-dimethyl derivatives of several compounds, including tryptamine, 5-hydroxytryptamine, 4-hydroxytryptamine, 5-methoxytryptamine, tyramine, and mescaline, were only about ten times less effective than lysergic acid, even though these compounds lack some of the ring systems of lysergic acid. The pattern of inhibition by related compounds with various substituents suggests that the antibody receptor site recognizes structural features resembling the LSD molecule. In particular, the aromatic nucleus and the dimethylated ethylamine side chain in phenylethylamine and tryptamine derivatives may assume in solution a conformation resembling ring A and the methylated nitrogen in ring C of LSD. Among the tryptamine derivatives, a large percentage of the most potent competitors are also psychotomimetic compounds. PMID:5283939

meso-4,4′-Dimeth­oxy-2,2′-{[(3aR,7aS)-2,3,3a,4,5,6,7,7a-octa­hydro-1H-benz­imidazole-1,3-di­yl]bis­(methyl­ene)}diphenol

PubMed Central

Rivera, Augusto; Quiroga, Diego; Ríos-Motta, Jaime; Kučeraková, Monika; Dušek, Michal

2013-01-01

The title compound, C23H30N2O4, a di-Mannich base derived from 4-meth­oxy­phenol and cis-1,2-di­amine­cyclo­hexane, has a perhydro­benzimidazolidine nucleus, in which the cyclo­hexane ring adopts a chair conformation and the heterocyclic ring has a half-chair conformation with a C—N—C—C torsion angles of −48.14 (15) and −14.57 (16)°. The mean plane of the heterocycle makes dihedral angles of 86.29 (6) and 78.92 (6)° with the pendant benzene rings. The mol­ecular structure of the title compound shows the presence of two inter­actions between the N atoms of the imidazolidine ring and the hydroxyl groups through intra­molecular O—H⋯N hydrogen bonds with graph-set motif S(6). The unobserved lone pairs of the N atoms are presumed to be disposed in a syn conformation, being only the second example of an exception to the typical ‘rabbit-ears’ effect in 1,2-di­amines. PMID:24046631

Comparison and usefulness of cardiac magnetic resonance versus computed tomography in infants six months of age or younger with aortic arch anomalies without deep sedation or anesthesia.

PubMed

Fogel, Mark A; Pawlowski, Thomas W; Harris, Matthew A; Whitehead, Kevin K; Keller, Marc S; Wilson, Justine; Tipton, Deanna; Harris, Christine

2011-07-01

The present project investigated whether cardiac magnetic resonance (CMR) of aortic arch anomalies can be performed successfully in infants <6 months of age without the use of cardiac anesthesia or deep sedation. We performed a retrospective review of infants ≤6 months old from 2005 to 2009 who underwent either CMR or computed tomography angiography to investigate aortic arch abnormalities. The CMR procedure used a "feed and swaddle" protocol without deep sedation or cardiac anesthesia. Of the 52 infants referred for CMR, 24 underwent the feed and swaddle protocol (aged 2.6 ± 1.4 months). One patient awoke during the study, and examination of the remaining 23 yielded a definitive diagnosis (success rate 96%). The scanning time was 6.2 ± 3.1 minutes, with the large airways evaluation accounting for 1/2 the time. Single-shot axial steady-state free precession, in which the definitive diagnosis was made, accounted for 0.59 ± 0.3 minutes. Fifteen infants were diagnosed with a vascular ring. Of the 8 infants who underwent surgery, the diagnostic accuracy was 100%. During the same period, 19 patients, who had undergone computed tomography angiography (aged 1.67 ± 1.20 months), were referred for aortic arch evaluation. Of these 19 patients, 6 (32%) underwent sedation or anesthesia. The imaging time was 0.08 ± 0.06 minutes, significantly different from the CMR times (p <0.01). However, the overall room times (31.3 ± 22.3 and 35.8 ± 3.86 minutes, respectively) were not different between the CMR and angiographic groups. The radiation dose was 1.41 ± 1.03 mSv. In conclusion, CMR evaluation of aortic arch anomalies in children <6 months old can be successfully completed quickly using a feed and swaddle approach with high diagnostic accuracy. This protocol avoids the risks of sedation, as well as the radiation associated with computed tomography angiography. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

PubMed Central

Nunes, A.D.C.; Souza, A.P.S.; Macedo, L.M.; Alves, P.H.; Pedrino, G.R.; Colugnati, D.B.; Mendes, E.P.; Santos, R.A.S.; Castro, C.H.

2017-01-01

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases. PMID:28355350

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.

PubMed

Nunes, A D C; Souza, A P S; Macedo, L M; Alves, P H; Pedrino, G R; Colugnati, D B; Mendes, E P; Santos, R A S; Castro, C H

2017-03-23

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Study of the effect of thiols on the vasodilatory potency of S-nitrosothiols by using a modified aortic ring assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giustarini, Daniela, E-mail: giustarini@unisi.it; Tsikas, Dimitrios, E-mail: tsikas.dimitros@mh-hannover.de; Rossi, Ranieri, E-mail: ranieri@unisi.it

2011-10-15

Both low-molecular-mass thiols (LMM-SH) and protein thiols (P-SH) can modulate the biological activity of S-nitrosothiols (RSNO) via S-transnitrosation reactions. It has been difficult to evaluate the entity of this effect in blood circulation by in vitro assays with isolated aorta rings so far, because media rich in proteins cannot be used due to the foaming as a consequence of the needed gas bubbling. We have modified the original apparatus for organ bioassay in order to minimize foaming and to increase analytical performance. By using this modified bioassay we investigated the vasodilatory potency of various endogenous RSNOs in the presence ofmore » physiologically relevant concentrations of albumin and LMM-SH. Our results show that the sulfhydryl group of the cysteine moiety of albumin and LMM-SH has a dramatic effect on the vasodilatory potency of RSNO. Considering the equilibrium constants for S-transnitrosation reactions and the concentration of P-SH and LMM-SH we measured in healthy humans (aged 18-85 years), we infer that the age-dependency of hematic levels of LMM-SH may have a considerable impact in RSNO-mediated vasodilation. S-Nitrosoproteins such as S-nitrosoalbumin may constitute a relatively silent and constant amount of circulating RSNO. On the other hand, LMM-SH may mediate and control the biological actions of S-nitrosoproteins via S-transnitrosation reactions, by forming more potent nitric oxide-releasing LMM-S-nitrosothiols. Lifestyle habits, status of health and individual age are proven factors that, in turn, may influence the concentration of these compounds. These aspects should be taken into consideration when testing the vasodilatory effects of RSNO in pre-clinical studies. - Highlights: > A modification of the organ chamber apparatus for aortic ring bioassays is proposed. > The new apparatus can work in the presence of albumin at physiological concentrations. > Potency of RSNOs was studied in the presence of albumin and low molecular mass -SH. > Plasma thiol levels decrease with age. > Potency of RSNOs varies in dependence of age and more in general of plasma thiol status.« less

Cardiovascular effects in vitro of aqueous extract of wild strawberry (Fragaria vesca, L.) leaves.

PubMed

Mudnic, I; Modun, D; Brizic, I; Vukovic, J; Generalic, I; Katalinic, V; Bilusic, T; Ljubenkov, I; Boban, M

2009-05-01

In contrast to the strawberry fruits, strawberry leaves as a source of bioactive compounds with potentially beneficial biological effects have been largely overlooked. In this study we examined direct, dose-dependent effects of wild strawberry (Fragaria vesca, L.) leaves aqueous extract, in two experimental models and animal species, the isolated guinea pig hearts and rat aortic rings. Vasodilatory potential of the wild strawberry leaves extract was compared with vasodilatory activity of aqueous extract of hawthorn (Crataegus oxycantha, L) leaves with flowers, which can be regarded as a reference plant extract with a marked vasodilatory activity. The extracts were analysed by their "phenolic fingerprints", total phenolic content and antioxidative capacity. Their vasodilatory activity was determined and compared in the isolated aortic rings from 24 rats that were exposed to the extracts doses of 0.06, 0.6, 6, and 60 mg/100ml. Both extracts induced similar, dose-dependent vasodilation. Maximal relaxation was 72.2+/-4.4% and 81.3+/-4.5%, induced by the strawberry and hawthorn extract, respectively. To determine vasodilatory mechanisms of the wild strawberry leaves extract, endothelium-denuded and intact rings exposed to nitric oxide (NO) synthase inhibitor L-NAME or cyclooxygenase inhibitor indomethacin were used. Removal of the endothelium prevented and exposure to L-NAME or indomethacin strongly diminished the vasodilatatory response to the extract. In the isolated hearts (n=12), the wild strawberry extract was applied at concentrations of 0.06, 0.18, 0.6, and 1.8 mg/100ml. Each dose was perfused for 3.5 min with 15 min of washout periods. Heart contractility, electrophysiological activity, coronary flow and oxygen consumption were continuously monitored. The extract did not significantly affect heart rate and contractility, main parameters of the cardiac action that determine oxygen demands, while coronary flow increased up to 45% over control value with a simultaneous decrease of oxygen extraction by 34%. The results indicate that the aqueous extract of wild strawberry leaves is a direct, endothelium-dependent vasodilator, action of which is mediated by NO and cyclooxygenase products and which potency is similar to that of the hawthorn aqueous extract.

Anti-angiogenic and vascular disrupting effects of C9, a new microtubule-depolymerizing agent

PubMed Central

Ren, Xuan; Dai, Mei; Lin, Li-Ping; Li, Pui-Kai; Ding, Jian

2009-01-01

Background and purpose: The critical role of blood supply in the growth of solid tumours makes blood vessels an ideal target for anti-tumour drug discovery. The anti-angiogenic and vascular disrupting activities of C9, a newly synthesized microtubule-depolymerizing agent, were investigated with several in vitro and in vivo models. Possible mechanisms involved in its activity were also assessed. Experimental approach: Microtubule-depolymerizing actions were assessed by surface plasmon resonance binding, competitive inhibition and cytoskeleton immunofluorescence. Anti-angiogenic and vascular disrupting activities were tested on proliferation, migration, tube formation with human umbilical vein endothelial cells, and in rat aortic ring, chick chorioallantoic membrane and Matrigel plug assays. Western blots and Rho activation assays were employed to examine the role of Raf-MEK-ERK (mitogen-activated ERK kinase, extracellular signal-regulated kinase) and Rho/Rho kinase signalling. Key results: C9 inhibited proliferation, migration and tube formation of endothelial cells and inhibited angiogenesis in aortic ring and chick chorioallantoic membrane assays. C9 induced disassembly of microtubules in endothelial cells and down-regulated Raf-MEK-ERK signalling activated by pro-angiogenic factors. In addition, C9 disrupted capillary-like networks and newly formed vessels in vitro and rapidly decreased perfusion of neovasculature in vivo. Endothelial cell contraction and membrane blebbing induced by C9 in neovasculature was dependent on the Rho/Rho kinase pathway. Conclusions and implications: Anti-angiogenic and vascular disruption by C9 was associated with changes in morphology and function of endothelial cells, involving the Raf-MEK-ERK and Rho/Rho kinase signalling pathways. These findings strongly suggest that C9 is a new microtubule-binding agent that could effectively target tumour vasculature. PMID:19302593

Homocysteine impaired endothelial function through compromised vascular endothelial growth factor/Akt/endothelial nitric oxide synthase signalling.

PubMed

Yan, Ting-Ting; Li, Qian; Zhang, Xuan-Hong; Wu, Wei-Kang; Sun, Juan; Li, Lin; Zhang, Quan; Tan, Hong-Mei

2010-11-01

1. Hyperhomocysteinaemia (HHcy) is associated with endothelial dysfunction and has been recognized as a risk factor of cardiovascular disease. The present study aimed to investigate the effect of homocysteine (Hcy) on endothelial function in vivo and in vitro, and the underlying signalling pathways. 2. The HHcy animal model was established by intragastric administration with l-methionine in rats. Plasma Hcy and nitric oxide (NO) concentration were measured by fluorescence immunoassay or nitrate reductase method, respectively. Vasorelaxation in response to acetylcholine and sodium nitroprusside were carried out on aortic rings. Human umbilical vein endothelial cells (HUVEC) were treated with indicated concentrations of Hcy in the in vitro experiments. Intracellular NO level and NO concentration in culture medium were assayed. The alterations of possible signalling proteins were detected by western blot analysis. 3. l-methionine administration induced a significant increase in plasma Hcy and decrease in plasma NO. Endothelium-dependent relaxation of aortic rings in response to acetylcholine was impaired in l-methionine-administrated rats. The in vitro study showed that Hcy reduced both intracellular and culture medium NO levels. Furthermore, Hcy decreased phosphorylation of endothelial nitric oxide synthase (eNOS) at serine-1177 and phosphorylation of Akt at serine-473. Hcy-induced dephosphorylation of eNOS at Ser-1177 was partially reversed by insulin (Akt activator) and GF109203X (PKC inhibitor). Furthermore, Hcy reduced vascular endothelial growth factor (VEGF) expression in a dose-dependent manner. 4. In conclusion, Hcy impaired endothelial function through compromised VEGF/Akt/endothelial nitric oxide synthase signalling. These findings will be beneficial for further understanding the role of Hcy in cardiovascular disease. © 2010 Blackwell Publishing Asia Pty Ltd.

Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: a critical role for heme oxygenase-1.

PubMed

Shen, Yu; Ward, Natalie C; Hodgson, Jonathan M; Puddey, Ian B; Wang, Yutang; Zhang, Di; Maghzal, Ghassan J; Stocker, Roland; Croft, Kevin D

2013-12-01

Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE(-/-) mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE(-/-) mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE(-/-) mice. Mechanistic studies revealed that HFD+Q significantly improved plasma F2-isoprostanes, 24h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE(-/-) mice (P<0.05). HFD+Q also resulted in small changes in plasma cholesterol (P<0.05 in WT) and plasma triacylglycerols (P<0.05 in ApoE (-/-)mice). In a separate experiment, quercetin did not protect against hypochlorite-induced endothelial dysfunction in arteries obtained from heterozygous HO-1 gene knockout mice with low expression of HO-1 protein. Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction and ApoE(-/-) mice against atherosclerosis. These effects are associated with improvements in nitric oxide bioavailability and are critically related to arterial induction of HO-1. © 2013 Elsevier Inc. All rights reserved.

Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

PubMed Central

Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

2014-01-01

Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

A low-dose atorvastatin and losartan combination directly improves aortic ring relaxation and diminishes ischaemic-reperfusion injury in isolated rat hearts

PubMed Central

Lunder, Mojca; Janić, Miodrag; Žiberna, Lovro; Drevenšek, Gorazd; Šabovič, Mišo

2012-01-01

Summary Background The cardiovascular pleiotropic effects of statins and angiotensin receptor blockers (ARBs) could be of interest for innovative preventive approaches. We aimed to investigate whether low-dose atorvastatin and losartan, separately not possessing protective cardiovascular pleiotropic effects, express them when combined. Material/Methods Forty-five adult male Wistar rats were anaesthetized and their thoracic aortas and hearts were isolated. Relaxation of aortic rings, coronary flow rate and the extent of myocardial ischaemic-reperfusion injury were measured. Different concentrations (0.01, 0.1, 1.0 μM) of atorvastatin and losartan added to a perfusion medium were first tested. The separate drugs, which were ineffective, were then combined at the same concentrations and the concentration was tested in the same model. Results Low concentrations of atorvastatin or losartan (0.1 and 1 μM, respectively) produced no effects in isolated aorta. However, surprisingly, when these drug concentrations were combined, a significantly improved endothelium-dependent relaxation of the thoracic aorta was observed. Similarly, when combining individually ineffective concentrations of atorvastatin or losartan (0.01 and 0.1 μM, respectively), significantly increased coronary flow and a decreased extent of myocardial injury were observed. By using a nitric oxide-synthase inhibitor, we demonstrated that the vasodilatory effects obtained were nitric oxide-dependent. The degree of effectiveness by the combination was comparable to that obtained by 10-fold (atorvastatin) or 100-fold (losartan) higher concentrations of the separate drugs. Conclusions Our results revealed that remarkable additive/synergistic effects exist between low-doses of a statin (atorvastatin) and an ARB (losartan), resulting in important cardiovascular protection. This new concept could be valuable in cardiovascular prevention. PMID:22936187

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.

PubMed

Silveira, Edna Aparecida; Siman, Fabiana Dayse Magalhães; de Oliveira Faria, Thaís; Vescovi, Marcos Vinícius Altoé; Furieri, Lorena Barros; Lizardo, Juliana Hott Fúcio; Stefanon, Ivanita; Padilha, Alessandra Simão; Vassallo, Dalton Valentim

2014-02-01

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Anti-Cancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogs

PubMed Central

Beedie, Shaunna L.; Peer, Cody J.; Pisle, Steven; Gardner, Erin R.; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H.; Vargesson, Neil; Figg, William D.

2015-01-01

Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenesis pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogs (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the anti-angiogenic properties of these newly synthesized compounds. We examined the specific anti-angiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. Additionally, further in vitro efficacy was evaluated using HUVECs and PC3 cells treated with 5μM and 10μM doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The anti-angiogenic properties of the compounds was also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, while Gu998 and Gu992 showed no difference. The compounds anti-tumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogs as a promising immunomodulatory class with anti-cancer effects that warrant further development to characterize their mechanisms of action. PMID:26269604

The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase.

PubMed

Di Santo, Stefano; Seiler, Stefanie; Fuchs, Anna-Lena; Staudigl, Jennifer; Widmer, Hans Rudolf

2014-01-01

Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

Evaluation of the in vitro and in vivo angiogenic effects of exendin-4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Hye-Min; Kang, Yujung; Chun, Hyung J.

2013-04-26

Highlights: •We investigated the effects of exendin-4 on the angiogenic process. •Exendin-4 increased migration, sprouting, and tube formation by HUVECs in in vitro. •Exendin-4 increased sprouts in aortic rings and induced new vessels in Matrigel in in vivo. •Exendin-4 may be of potential use for the treatment of vascular complications of diabetes. -- Abstract: Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was reported to induce the proliferation of endothelial cells. However, its angiogenic effect on endothelial cells has not been clearly evaluated. Therefore, we investigated the effectsmore » of exendin-4 on the angiogenic process with respect to migration, sprouting, and neovascularization using in vitro and in vivo assays. Treatment with exendin-4 increased the migration of human umbilical vein endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays. These responses were abolished by co-treatment with exendin (9–39), a GLP-1 receptor antagonist, which suggests that exendin-4 regulates endothelial cell migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo assay, treatment of aortic rings with exendin-4 increased the sprouting of endothelial cells. Exendin-4 also significantly increased the number of new vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in vivo assays and provide a mechanism underlying the cardioprotective effects of exendin-4.« less

Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke.

PubMed

Conklin, Daniel J; Haberzettl, Petra; Prough, Russell A; Bhatnagar, Aruni

2009-05-01

Exposure to tobacco smoke impairs endothelium-dependent arterial dilation. Reactive constituents of cigarette smoke are metabolized and detoxified by glutathione-S-transferases (GSTs). Although polymorphisms in GST genes are associated with the risk of cancer in smokers, the role of these enzymes in regulating the cardiovascular effects of smoking has not been studied. The P isoform of GST (GSTP), which catalyzes the conjugation of electrophilic molecules in cigarette smoke such as acrolein, was expressed in high abundance in the mouse lung and aorta. Exposure to tobacco smoke for 3 days (5 h/day) decreased total plasma protein. These changes were exaggerated in GSTP(-/-) mice. Aortic rings isolated from tobacco smoke-exposed GSTP(-/-) mice showed greater attenuation of ACh-evoked relaxation than those from GSTP(+/+) mice. The lung, plasma, and aorta of mice exposed to tobacco smoke or acrolein (for 5 h) accumulated more acrolein-adducted proteins than those tissues of mice exposed to air, indicating that exposure to tobacco smoke results in the systemic delivery of acrolein. Relative to GSTP(+/+) mice, modification of some proteins by acrolein was increased in the aorta of GSTP(-/-) mice. Aortic rings prepared from GSTP(-/-) mice that inhaled acrolein (1 ppm, 5 h/day for 3 days) or those exposed to acrolein in an organ bath showed diminished ACh-induced arterial relaxation more strongly than GSTP(+/+) mice. Acrolein-induced endothelial dysfunction was prevented by pretreatment of the aorta with N-acetylcysteine. These results indicate that GSTP protects against the endothelial dysfunction induced by tobacco smoke exposure and that this protection may be related to the detoxification of acrolein or other related cigarette smoke constituents.

Insights from diversified anti-angiogenic models: Role of β-interferon inducer DEAE-Dextran.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Patel, Snehal S

2018-04-17

Angiogenesis, the physiological process involving growth of new blood vessels from preexisting vessels, is essential for organ growth and repair. However, the imbalance in angiogenesis contributes to copious pathologies including cancer. Preceding the development of anti-angiogenic or proangiogenic agents, its evaluation is equally imperative; hence, precise and adequate models required. Valid mammalian models are expensive, time-consuming and not easy to set up, instigating legal and ethical aspects making it necessary to establish models with satisfactory activity and limited drawbacks. We investigated the activity of DEAE-Dextran on diversified models viz. in vitro cell migration assay, ex vivo aortic ring assay, in vitro chick yolk sac membrane assay and in vivo matrigel plug xenograft model corroborating its anti-angiogenic potential and establishing the best means of evaluation. Assorted models were reproducible and correlative to one another. DEAE-Dextran exhibited excellent anti-angiogenic effect in cell migration assay over a duration of 24 h compared to the vehicle control fibroblast cell line and aortic ring possessed an alleviated rate of sprouting when treated with DEAE-Dextran with contrast to vehicle control aorta. Similarly, decreased vascular density was observed in DEAE-Dextran treated chick embryos implicating potency of the β-interferon inducer. Augmenting to these results, the matrigel plugs also mitigated vascular net as well as reduced levels of angiogenic marker CD31. Substantially, DEAE-Dextran leads to anti-tumor activity through anti-angiogenic action and a combination of in vitro and in vivo model is vital for the judgement of anti-angiogenic potential since an in vitro model exempts mammalian-culture considerations. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

PubMed

Zhu, Yanna; Xia, Min; Yang, Yan; Liu, Fengqiong; Li, Zhongxia; Hao, Yuantao; Mi, Mantian; Jin, Tianru; Ling, Wenhua

2011-11-01

Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.

PubMed

Chen, Young-Bin; Lan, Ying-Wei; Hung, Tsai-Hsien; Chen, Lih-Geeng; Choo, Kong-Bung; Cheng, Winston T K; Lee, Hsuan-Shu; Chong, Kowit-Yu

2015-07-01

Several studies of stem cell-based gene therapy have indicated that long-lasting regeneration following vessel ischemia may be stimulated through VEGFA gene therapy and/or MSC transplantation for reduction of ischemic injury in limb ischemia and heart failure. The therapeutic potential of MSC transplantation can be further improved by genetically modifying MSCs with genes which enhance angiogenesis following ischemic injury. In the present study, we aimed to develop an approach in MSC-based therapy for repair and mitigation of ischemic injury and regeneration of damaged tissues in ischemic disease. HSP70 promoter-driven VEGFA expression was induced by resveratrol (RSV) in MSCs, and in combination with known RSV biological functions, the protective effects of our approach were investigated by using ex vivo aortic ring coculture system and a 3D scaffolds in vivo model. Results of this investigation demonstrated that HSP promoter-driven VEGFA expression in MSC increased approximately 2-fold over the background VEGFA levels upon HSP70 promoter induction by RSV. Exposure of HUVEC cells to medium containing MSC in which VEGFA had been induced by cis-RSV enhanced tube formation in the treated HUVEC cells. RSV-treated MSC cells differentiated into endothelial-like phenotypes, exhibiting markedly elevated expression of endothelial cell markers. These MSCs also induced aortic ring sprouting, characteristic of neovascular formation from pre-existing vessels, and additionally promoted neovascularization at the MSC transplantation site in a mouse model. These observations support a hypothesis that VEGFA expression induced by cis-RSV acting on the HSP70 promoter in transplanted MSC augments the angiogenic effects of stem cell gene therapy. The use of an inducible system also vastly reduces possible clinical risks associated with constitutive VEGFA expression.

Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice

PubMed Central

Li, Weijuan; Chen, Yaoqi; Li, Songhai; Guo, Xiaopeng; Zhou, Wenping; Zeng, Qiutang; Liao, Yuhua; Wei, Yumiao

2014-01-01

This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-α, nuclear factor-kappa B (NF-κB) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-κB and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-κB. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis. PMID:25628779

The effect of hirudin modification of silk fibroin on cell growth and antithrombogenicity.

PubMed

Wang, Qiongyu; Tu, Fangfang; Liu, Yunfei; Zhang, Yujin; Li, Helei; Kang, Zhao; Yin, Yin; Wang, Jiannan

2017-06-01

Thrombus formation remains a particular challenge for small-diameter vascular grafts. In this study, the direct thrombin inhibitor hirudin (Hir) was used to modify silk fibroin films in an attempt to enhance its antithrombogenic properties. Hir was successfully attached to silk fibroin and uniformly distributed in the regenerative material. Hir-modified films showed good cytocompatibility, and supported adhesion and proliferation of fibroblasts (L929), human umbilical vascular endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs). Proliferation of HAVSMCs was inhibited by increasing Hir concentration. Activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT) of Hir-modified silk fibroin tubular scaffolds (SFTSs) were all increased markedly compared with fresh rabbit blood, ethanol-treated SFTS and unmodified SFTS, demonstrating the improved antithrombogenicity of SFTSs following modification with Hir. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of nitric oxide in the mediation of the hypotensive action of the essential oil of Mentha x villosa in normotensive conscious rats.

PubMed

Lahlou, Saad; Magalhães, Pedro Jorge Caldas; Carneiro-Leão, Ricardo Ferreira Lima; Leal-Cardoso, José Henrique

2002-08-01

Recently, we showed that intravenous (i.v.) treatment with the essential oil of Mentha x villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood pressure; the effect occurred independently of the presence of an operational central autonomic drive to the cardiovascular system. This finding suggested that the hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle. The present study examines this possibility and whether EOMV-induced hypotension is mediated, at least in part, by an endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced partially, but significantly, the maximal percent decreases in MAP elicited by EOMV without affecting the bradycardia. In rat isolated thoracic aorta preparations, EOMV (1 - 130 microg/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant activity of EOMV was significantly reduced by the incubation of endothelium-intact rings with L-NAME (20 microM), as evidenced by the significant enhancement in the IC50 for EOMV-induced reduction of potassium-induced contraction (133.8 +/- 26.5 vs. 65.2 +/- 8.2 microg/ml in the absence of L-NAME). Furthermore, the vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also significantly reduced (IC50 = 109 +/- 10 microg/ml), compared to those observed in segments with intact endothelium (IC50 = 61 +/- 13 microg/ml). These results show that i.v. treatment with EOMV dose-dependently decreases blood pressure in conscious rats, and that this action is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells appears partially involved in the aortic relaxation induced by EOMV and in turn in the mediation of EOMV-induced hypotension. They further support the concept that EOMV-induced hypotension and bradycardia occurred independently.

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

PubMed

Lee, Candice Y; Wong, Joshua K; Ross, Ronald E; Liu, David C; Khabbaz, Kamal R; Martellaro, Angelo J; Gorea, Heather R; Sauer, Jude S; Knight, Peter A

Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells.

PubMed

Park, Il Hwan; Hwang, Hye Mi; Jeon, Byeong Hwa; Kwon, Hyung-Joo; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

2015-06-12

Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-θ (PKCθ) and protein kinase C-β (PKCβ) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCθ and PKCβ stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox(-/-) mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.

Ultra-low profile Ovation device: is it the definitive solution for EVAR?

PubMed

de Donato, G; Setacci, F; Sirignano, P; Galzerano, G; Borrelli, M P; di Marzo, L; Setacci, C

2014-02-01

When Juan Parodi implanted an endograft in a human body for the first time on September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade device was primitive, extremely rigid, and had a bulky profile of 27 French (F). Since then, stent-graft technology has evolved rapidly, limitations of earlier-generation devices have been overtaken, and endovascular aneurysm repair (EVAR) eligibility has increased enormously. Nevertheless (still) challenging aortoiliac anatomy such as short and complex proximal aortic neck seal zones and narrow access vessels are responsible for EVAR ineligibility in up to 50% of cases. The Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA, USA) is a trimodular device designed with the aortic body delivered via a flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter - OD). The aortic body is provided with a suprarenal nitinol stent with anchors that provide active fixation, while a network of rings and channels that are inflated with a low-viscosity radiopaque polymer during stent-graft deployment, provides effective sealing. The previous EVAR technology aimed to both anchor and seal using stents combined with fabric, with neither optimized for their roles and each forced to compete for the same space within their delivery catheters, which inevitably led to larger profile of the delivery system. The technical revolution of the Ovation endograft includes the idea to truly uncouple the stages of stent-graft fixation and seal during the procedure. In the Ovation endograft platform, stent and fabric are not competing the same space within the delivery system and an ultra-low profile delivery can be achieved without compromise. With such a low-profile delivery catheter, approximately 90% of men and 70% of women with abdominal aortic aneurysm have access vessel diameters considered fit for endovascular repair. The aim of this review paper was to analyze the main properties of Ovation endograft, to emphasize the advantage of the ultra-low profile device, and to sum up current literature.

Antioxidant Effect of Captopril and Enalapril on Reactive Oxygen Species-Induced Endothelial Dysfunction in the Rabbit Abdominal Aorta

PubMed Central

Kim, Ji Hoon; Kim, Young Hak; Chung, Won-Sang; Suh, Jung Kook; Kim, Sung Jin

2013-01-01

Background Reactive oxygen species (ROS) are known to be related to cardiovascular diseases. Many studies have demonstrated that angiotensin-converting enzyme inhibitors have beneficial effects against ROS. We investigated the antioxidant effect of captopril and enalapril in nitric oxide mediated vascular endothelium-dependent relaxations. Materials and Methods Isolated rabbit abdominal aorta ring segments were exposed to ROS by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (range, 10-5 to 3×10-4 M) of captopril and enalapril. Before and after electrolysis, the endothelial function was measured by preconstricting the vessels with norepinephrine (10-6 M) followed by the cumulative addition of acetylcholine (range, 3×10-8 to 10-6 M). The relevance of the superoxide anion and hydrogen peroxide scavenging effect of captopril and enalapril was investigated using additional pretreatments of diethyldithiocarbamate (DETCA, 0.5 mM), an inhibitor of Cu/Zn superoxide dismutase, and 3-amino-1,2,4-triazole (3AT, 50 mM), an inhibitor of catalase. Results Both captopril and enalapril preserved vascular endothelium-dependent relaxation after exposure to ROS in a dose-dependent manner (p<0.0001). Pretreatment with DETCA attenuated the antioxidant effect of captopril and enalapril (p<0.0001), but pretreatment with 3AT did not have an effect. Conclusion Both captopril and enalapril protect endothelium against ROS in a dose-dependent fashion in isolated rabbit abdominal aortas. This protective effect is related to superoxide anion scavenging. PMID:23422724

In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery.

PubMed

Maulvi, Furqan A; Lakdawala, Dhara H; Shaikh, Anjum A; Desai, Ankita R; Choksi, Harsh H; Vaidya, Rutvi J; Ranch, Ketan M; Koli, Akshay R; Vyas, Bhavin A; Shah, Dinesh O

2016-03-28

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Murine study of portal hypertension associated endothelin-1 hypo-response.

PubMed

Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas

2015-04-28

To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group. Abdominal aortic flow was reduced by 19% ± 9%, 32% ± 10% and 9% ± 9% in wild type, eNOS(-/-) and iNOS(-/-) mice respectively. Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent. Moreover, portal hypertension in the portal vein ligation model is independent of ET-1 function.

Quantification of atherosclerosis with MRI and image processing in spontaneously hyperlipidemic rabbits.

PubMed

Hänni, Mari; Edvardsson, H; Wågberg, M; Pettersson, K; Smedby, O

2004-01-01

The need for a quantitative method to assess atherosclerosis in vivo is well known. This study tested, in a familiar animal model of atherosclerosis, a combination of magnetic resonance imaging (MRI) and image processing. Six spontaneously hyperlipidemic (Watanabe) rabbits were examined with a knee coil in a 1.5-T clinical MRI scanner. Inflow angio (2DI) and proton density weighted (PDW) images were acquired to examine 10 cm of the aorta immediately cranial to the aortic bifurcation. Examination of the thoracic aorta was added in four animals. To identify the inner and outer boundary of the arterial wall, a dynamic contour algorithm (Gradient Vector Flow snakes) was applied to the 2DI and PDW images, respectively, after which the vessel wall area was calculated. The results were compared with histopathological measurements of intima and intima-media cross-sectional area. The correlation coefficient between wall area measurements with MRI snakes and intima-media area was 0.879 when computed individual-wise for abdominal aortas, 0.958 for thoracic aortas, and 0.834 when computed segment-wise. When the algorithm was applied to the PDW images only, somewhat lower correlations were obtained. The MRI yielded significantly higher values than histopathology, which excludes the adventitia. Magnetic resonance imaging, in combination with dynamic contours, may be a suitable technique for quantitative assessment of atherosclerosis in vivo. Using two sequences for the measurement seems to be superior to using a single sequence.

Endothelial Estrogen Receptor-α Does Not Protect Against Vascular Stiffness Induced by Western Diet in Female Mice.

PubMed

Manrique, Camila; Lastra, Guido; Ramirez-Perez, Francisco I; Haertling, Dominic; DeMarco, Vincent G; Aroor, Annayya R; Jia, Guanghong; Chen, Dongqing; Barron, Brady J; Garro, Mona; Padilla, Jaume; Martinez-Lemus, Luis A; Sowers, James R

2016-04-01

Consumption of a diet high in fat and refined carbohydrates (Western diet [WD]) is associated with obesity and insulin resistance, both major risk factors for cardiovascular disease (CVD). In women, obesity and insulin resistance abrogate the protection against CVD likely afforded by estrogen signaling through estrogen receptor (ER)α. Indeed, WD in females results in increased vascular stiffness, which is independently associated with CVD. We tested the hypothesis that loss of ERα signaling in the endothelium exacerbates WD-induced vascular stiffening in female mice. We used a novel model of endothelial cell (EC)-specific ERα knockout (EC-ERαKO), obtained after sequential crossing of the ERα double floxed mice and VE-Cadherin Cre-recombinase mice. Ten-week-old females, EC-ERαKO and aged-matched genopairs were fed either a regular chow diet (control diet) or WD for 8 weeks. Vascular stiffness was measured in vivo by pulse wave velocity and ex vivo in aortic explants by atomic force microscopy. In addition, vascular reactivity was assessed in isolated aortic rings. Initial characterization of the model fed a control diet did not reveal changes in whole-body insulin sensitivity, aortic vasoreactivity, or vascular stiffness in the EC-ERαKO mice. Interestingly, ablation of ERα in ECs reduced WD-induced vascular stiffness and improved endothelial-dependent dilation. In the setting of a WD, endothelial ERα signaling contributes to vascular stiffening in females. The precise mechanisms underlying the detrimental effects of endothelial ERα in the setting of a WD remain to be elucidated.

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

PubMed

Wong, Nikki L; Achike, Francis I

2010-08-09

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Vorticity dynamics in an intracranial aneurysm

NASA Astrophysics Data System (ADS)

Le, Trung; Borazjani, Iman; Sotiropoulos, Fotis

2008-11-01

Direct Numerical Simulation is carried out to investigate the vortex dynamics of physiologic pulsatile flow in an intracranial aneurysm. The numerical solver is based on the CURVIB (curvilinear grid/immersed boundary method) approach developed by Ge and Sotiropoulos, J. Comp. Physics, 225 (2007) and is applied to simulate the blood flow in a grid with 8 million grid nodes. The aneurysm geometry is extracted from MRI images from common carotid artery (CCA) of a rabbit (courtesy Dr.Kallmes, Mayo Clinic). The simulation reveals the formation of a strong vortex ring at the proximal end during accelerated flow phase. The vortical structure advances toward the aneurysm dome forming a distinct inclined circular ring that connects with the proximal wall via two long streamwise vortical structures. During the reverse flow phase, the back flow results to the formation of another ring at the distal end that advances in the opposite direction toward the proximal end and interacts with the vortical structures that were created during the accelerated phase. The basic vortex formation mechanism is similar to that observed by Webster and Longmire (1998) for pulsed flow through inclined nozzles. The similarities between the two flows will be discussed and the vorticity dynamics of an aneurysm and inclined nozzle flows will be analyzed.This work was supported in part by the University of Minnesota Supercomputing Institute.

The urea decomposition product cyanate promotes endothelial dysfunction

PubMed Central

El-Gamal, Dalia; Rao, Shailaja Prabhakar; Holzer, Michael; Hallström, Seth; Haybaeck, Johannes; Gauster, Martin; Wadsack, Christian; Kozina, Andrijana; Frank, Saša; Schicho, Rudolf; Schuligoi, Rufina; Heinemann, Akos; Marsche, Gunther

2014-01-01

The dramatic cardiovascular mortality of chronic kidney disease patients is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate - promoting protein carbamylation at levels observed in uremic patients - attenuated arterial vasorelaxation of aortic rings in response to acetylcholine, without affecting sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. These data provide evidence that cyanate compromises endothelial functionality in vitro and in vivo and may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease. PMID:24940796

OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis.

PubMed

Sumi, Makoto; Sata, Masataka; Hashimoto, Ayako; Imaizumi, Takashi; Yanaga, Katsuhiko; Ohki, Takao; Mori, Toyoki; Nagai, Ryozo

2007-05-01

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.

GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist

PubMed Central

Wilson, Richard J; Giblin, Gerard M P; Roomans, Susan; Rhodes, Sharron A; Cartwright, Kerri-Ann; Shield, Vanessa J; Brown, Jason; Wise, Alan; Chowdhury, Jannatara; Pritchard, Sara; Coote, Jim; Noel, Lloyd S; Kenakin, Terry; Burns-Kurtis, Cynthia L; Morrison, Valerie; Gray, David W; Giles, Heather

2006-01-01

N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl}benzene sulphonamide (GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptors with additional human TP receptor affinity. At recombinant human prostanoid EP4 receptors expressed in HEK293 cells, GW627368X produced parallel rightward shifts of PGE2 concentration–effect (E/[A]) curves resulting in an affinity (pKb) estimate of 7.9±0.4 and a Schild slpoe not significantly different from unity. The affinity was independent of the agonist used. In rings of phenylephrine precontracted piglet saphenous vein, GW627368X (30–300 nM) produced parallel rightward displacement of PGE2 E/[A] curves (pKb=9.2±0.2; slope=1). GW627368X appears to bind to human prostanoid TP receptors but not the TP receptors of other species. In human washed platelets, GW627368X (10 μM) produced 100% inhibition of U-46619 (EC100)-induced aggregation (approximate pA2 ∼7.0). However, in rings of rabbit and piglet saphenous vein and of guinea-pig aorta GW627368X (10 μM) did not displace U-46619 E/[A] curves indicating an affinity of <5.0 for rabbit and guinea-pig prostanoid TP receptors. In functional assays GW627368X is devoid of both agonism and antagonist affinity for prostanoid CRTH2, EP2, EP3, IP and FP receptors. At prostanoid EP1 receptors, GW627368X was an antagonist with a pA2 of 6.0, and at prostanoid IP receptors the compound increased the maximum effect of iloprost by 55%. At rabbit prostanoid EP2 receptors the pA2 of GW627368X was <5.0. In competition radioligand bioassays, GW627368X had affinity for human prostanoid EP4 and TP receptors (pKi=7.0±0.2 (n=10) and 6.8 (n=2), respectively). Affinity for all other human prostanoid receptors was <5.3. GW627368X will be a valuable tool to explore the role of the prostanoid EP4 receptor in many physiological and pathological settings. PMID:16604093

Macroscopic anatomy of the great vessels and structures associated with the heart of the ringed seal (Pusa hispida).

PubMed

Smodlaka, H; Henry, R W; Reed, R B

2009-06-01

The ringed seal [Pusa (Phoca) hispida], as well as other seals, exhibits unique anatomical properties when compared to its terrestrial counterparts. In the ringed seal, the most conspicuous marine adaptation is the aortic bulb. This large dilatation of the ascending aorta is comparable to that found in other seal species and marine mammals. The branches of the ascending aorta (brachiocephalic trunk, left common carotid artery and left subclavian artery) are similar to those of higher primates and man. The peculiarities of the venous system are: three pulmonary veins, a pericardial venous plexus, a caval sphincter, a hepatic sinus with paired caudal vena cavae and a large extradural venous plexus. Generally, three common pulmonary veins (right, left and caudal) empty into the left atrium. The pericardial venous plexus lies deep to the mediastinal pericardial pleura (pleura pericardica) on the auricular (ventral) surface of the heart. The caval sphincter surrounds the caudal vena cava as it passes through the diaphragm. Caudal to the diaphragm, the vena cava is dilated (the hepatic sinus), and near the cranial extremity of the kidneys, it becomes biphid. The azygos vein is formed from the union of the right and left azygos veins at the level of the 5th thoracic vertebra. Cardiovascular physiological studies show some of these anatomical variations, especially of the venous system and the ascending aorta, to be modifications for diving. This investigation documents the large blood vessels associated with the heart and related structures in the ringed seal.

Use of 3D models of vascular rings and slings to improve resident education.

PubMed

Jones, Trahern W; Seckeler, Michael D

2017-09-01

Three-dimensional (3D) printing is a manufacturing method by which an object is created in an additive process, and can be used with medical imaging data to generate accurate physical reproductions of organs and tissues for a variety of applications. We hypothesized that using 3D printed models of congenital cardiovascular lesions to supplement an educational lecture would improve learners' scores on a board-style examination. Patients with normal and abnormal aortic arches were selected and anonymized to generate 3D printed models. A cohort of pediatric and combined pediatric/emergency medicine residents were then randomized to intervention and control groups. Each participant was given a subjective survey and an objective board-style pretest. Each group received the same 20-minutes lecture on vascular rings and slings. During the intervention group's lecture, 3D printed physical models of each lesion were distributed for inspection. After each lecture, both groups completed the same subjective survey and objective board-style test to assess their comfort with and postlecture knowledge of vascular rings. There were no differences in the basic demographics of the two groups. After the lectures, both groups' subjective comfort levels increased. Both groups' scores on the objective test improved, but the intervention group scored higher on the posttest. This study demonstrated a measurable gain in knowledge about vascular rings and pulmonary artery slings with the addition of 3D printed models of the defects. Future applications of this teaching modality could extend to other congenital cardiac lesions and different learners. © 2017 Wiley Periodicals, Inc.

Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside.

PubMed

Saxon, John T; Allen, Keith B; Cohen, David J; Chhatriwalla, Adnan K

2018-01-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient-prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient-prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions.

Metabolism of bepridil in laboratory animals and humans.

PubMed

Wu, W N; Hills, J F; Chang, S Y; Ng, K T

1988-01-01

The metabolism of bepridil was studied in the Swiss mouse, Sprague-Dawley rat, New Zealand rabbit, rhesus monkey, and healthy human. After oral administration of bepridil-14C-hydrochloride, recoveries of total radioactivity in urine and feces (7 days) were greater than or equal to 80% of the administered dose in all five species. Bepridil and 25 metabolites have been isolated by HPLC and TLC from representative plasma, urine, and fecal extract pools from all species and identified on the basis of TLC, HPLC, and mass spectrometry. The identified metabolites explained 60-99% of the total radioactivity in each sample for rabbit plasma, in which only 17% of the total radioactivity was characterized. Metabolic pathways involving oxidative reactions at seven sites on the bepridil molecule are proposed for each species. Metabolite formation in the five species is described by four interrelated pathways. The metabolic pathway involving aromatic hydroxylation followed by N-dealkylation, N-debenzylation, and N-acetylation was important in all species. Major metabolites produced by this pathway included 4-hydroxy(at N-phenyl)-bepridil (Ia), N-benzyl-4-amino-phenol (IV), and N-acetyl-4-aminophenol (Vy). Metabolite Ia was isolated in significant amounts (greater than or equal to 5% of sample) in all fecal and urine samples except rat urine. Metabolite IV was a major circulating metabolite in all species and a major urinary metabolite in humans. Metabolite Vy was present in significant quantities in urine in all species except rabbit. Other important pathways involved primary reactions such as iso-butyl hydroxylation, pyrrolidine ring oxidation, and N-debenzylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular causes of airway compression.

PubMed

Kussman, Barry D; Geva, Tal; McGowan, Francis X

2004-01-01

Compression of the paediatric airway is a relatively common and often unrecognized complication of congenital cardiac and aortic arch anomalies. Airway obstruction may be the result of an anomalous relationship between the tracheobronchial tree and vascular structures (producing a vascular ring) or the result of extrinsic compression caused by dilated pulmonary arteries, left atrial enlargement, massive cardiomegaly, or intraluminal bronchial obstruction. A high index of suspicion of mechanical airway compression should be maintained in infants and children with recurrent respiratory difficulties, stridor, wheezing, dysphagia, or apnoea unexplained by other causes. Prompt diagnosis is required to avoid death and minimize airway damage. In addition to plain chest radiography and echocardiography, diagnostic investigations may consist of barium oesophagography, magnetic resonance imaging (MRI), computed tomography, cardiac catheterization and bronchoscopy. The most important recent advance is MRI, which can produce high quality three-dimensional reconstruction of all anatomic elements allowing for precise anatomic delineation and improved surgical planning. Anaesthetic technique will depend on the type of vascular ring and the presence of any congenital heart disease or intrinsic lesions of the tracheobronchial tree. Vascular rings may be repaired through a conventional posterolateral thoracotomy, or utilizing video-assisted thoracoscopic surgery (VATS) or robotic endoscopic surgery. Persistent airway obstruction following surgical repair may be due to residual compression, secondary airway wall instability (malacia), or intrinsic lesions of the airway. Simultaneous repair of cardiac defects and vascular tracheobronchial compression carries a higher risk of morbidity and mortality.

Multiphoton microscopy observations of 3D elastin and collagen fiber microstructure changes during pressurization in aortic media.

PubMed

Sugita, Shukei; Matsumoto, Takeo

2017-06-01

Elastin and collagen fibers play important roles in the mechanical properties of aortic media. Because knowledge of local fiber structures is required for detailed analysis of blood vessel wall mechanics, we investigated 3D microstructures of elastin and collagen fibers in thoracic aortas and monitored changes during pressurization. Using multiphoton microscopy, autofluorescence images from elastin and second harmonic generation signals from collagen were acquired in media from rabbit thoracic aortas that were stretched biaxially to restore physiological dimensions. Both elastin and collagen fibers were observed in all longitudinal-circumferential plane images, whereas alternate bright and dark layers were observed along the radial direction and were recognized as elastic laminas (ELs) and smooth muscle-rich layers (SMLs), respectively. Elastin and collagen fibers are mainly oriented in the circumferential direction, and waviness of collagen fibers was significantly higher than that of elastin fibers. Collagen fibers were more undulated in longitudinal than in radial direction, whereas undulation of elastin fibers was equibiaxial. Changes in waviness of collagen fibers during pressurization were then evaluated using 2-dimensional fast Fourier transform in mouse aortas, and indices of waviness of collagen fibers decreased with increases in intraluminal pressure. These indices also showed that collagen fibers in SMLs became straight at lower intraluminal pressures than those in EL, indicating that SMLs stretched more than ELs. These results indicate that deformation of the aorta due to pressurization is complicated because of the heterogeneity of tissue layers and differences in elastic properties of ELs, SMLs, and surrounding collagen and elastin.

Detection of atheroma using Photofrin IIr and laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; Papazoglou, Theodore G.; van der Veen, Maurits J.; Papaioannou, Thanassis; Fishbein, Michael C.; Chandra, Mudjianto; Beeder, Clain; Shi, Wei-Qiang; Grundfest, Warren S.

1991-06-01

The goal of this study was to investigate laser induced fluorescence spectroscopy (LIFS) as a method of localization of atherosclerotic lesions not visible by angiography using Photofrin IIr enhanced fluorescence. Twenty-four New Zealand White rabbits divided into six groups varying in type of arterial wall lesion and Photofrin IIr administration time (i.v.) were used. Aortic wall fluorescence signals were acquired from the aortic arch to iliac bifurcation. The output of a He-Cd laser (442 nm, 17 mW) was directed at the arterial wall through a 400 micron fiber. The fluorescence signal created in the arterial wall was collected via the same fiber and analyzed by an optical multi-channel analyzer (OMA). The ratio of fluorescence intensities at 630 nm (Photofrin IIr) and 540 nm (autofluorescence of artery wall) was analyzed (I630nm/I540nm). Intensity ratio values 24 hours after administration of Photofrin IIr were found to be as follows: in normal artery wall of 0.30 +/- 0.14 (n equals 3), in mechanically damaged wall of 0.91 +/- 0.65 (n equals 2) and, in atheromatous tissue, 0.88 +/- 0.54 (n equals 4). The intensity ratio of atheromatous tissue without Photofrin IIr was 0.23 +/- 0.04 (n equals 7). These results suggest that the use of Photofrin IIr allows in vivo atheroma detection by LIFS because of its ability to accumulate in atheroma. In addition, accumulation of Photofrin IIr was found in artery walls traumatized by balloon catheter intervention. Using this method, a catheter-based LIFS system may be developed for atheroma detection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruszyna, H.; Kruszyna, R.; Hurst, J.

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55; dichlorobis(2,2'-dipyridyl)ruthenium(II) 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occuring in 4 to 7 d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be duemore » to the metal and not to its associated ligands. Only complexes having a nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic argonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominum when these isolated muscles had been contracted by acetylcholine. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimllylethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.« less

Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production

PubMed Central

Martin, Sophie; Andriambeloson, Emile; Takeda, Ken; Andriantsitohaina, Ramaroson

2002-01-01

The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca2+ mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols™, and delphinidin, an anthocyanin were used. RWPC stimulated a Ca2+-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. RWPC, Provinols™ and delphinidin increased cytosolic free calcium ([Ca2+]i), by releasing Ca2+ from intracellular stores and by increasing Ca2+ entry. The RWPC-induced increase in [Ca2+]i was decreased by exposure to ryanodine (30 μM), whereas Provinols™ and delphinidin-induced increases in [Ca2+]i were decreased by bradykinin (0.1 μM) and thapsigargin (1 μM) pre-treatment. RWPC, Provinols™ and delphinidin-induced increases in [Ca2+]i were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 μM) and tyrosine kinase (herbimycin A, 1 μM). RWPC, Provinols™ and delphinidin induced herbimycin A (1 μM)-sensitive tyrosine phosphorylation of several intracellular proteins. Provinols™ released Ca2+ via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca2+ only via a PTX-sensitive mechanism. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca2+]i and the activation of tyrosine kinases. Furthermore, RWPC, Provinols™ and delphinidin display differences in the process leading to [Ca2+]i increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds. PMID:11906973

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

PubMed

Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

2018-03-08

Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007). Circumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Effects of chronic administration of ethanolic extract of kolanut (Cola nitida) and caffeine on vascular function.

PubMed

Salahdeen, H M; Omoaghe, A O; Isehunwa, G O; Murtala, B A; Alada, A R A

2014-03-01

Kolanut (Cola nitida) is consumed in virtually every part of the world. The caffeine content of kolanut is scarce and the number of investigations studying the health benefits of kolanut is negligible compared to coffee. The present study was designed to identify the caffeine content of kolanut and evaluate the effect of its chronic consumption on cardiovascular functions in rats. The caffeine content of kolanut was determined by Gas chromatography-mass spectrometry (GC-MS). Wistar albino rats were divided into four groups (10 Rats/group). Kolanut extract (11.9 mg/kg), caffeine extracted from kolanut (7.5 mg/kg), decaffeinated of kolanut extract (6 mg/kg) and distilled water (control) was administered orally to each group for six-weeks. Effect of treatment on body weight, blood pressure and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) of the aortic rings was assessed. The total caffeine content of kolanut extract was found to be 51% and it was 96% pure from GC-MS analysis. Chronic consumption of kolanut and caffeine significantly (p < 0.05) decreased body weight. Similarly, kolanut extract decaffeinated kolanut and caffeine significantly (p < 0.05) reduced the contractile response to noradrenaline and higher potassium solution. Kolanut extract and caffeine also significantly (p < 0.05) increased the mean arterial blood pressure. Caffeine and kolanut consumption reduced the relaxation response to both acetylcholine and sodium nitroprusside. Atropine and L-NAME considerably inhibit the ACh-induced relaxation of the rat aortic ring suggesting the involvement of cholinergic mechanism. However, indomethacin (10(-4)M) also attenuated the ACh response indicating involvement of protanoids. The results suggest that treatment with both kolanut extract and caffeine had similar characteristics between the two groups with no significant differences in the ACh-induced relaxation of thering suggesting that the action of kolanut extract is due to its caffeine content.

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta

NASA Technical Reports Server (NTRS)

Papadopoulos, Anthony; Delp, Michael D.

2003-01-01

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.

The effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth in squamous cell carcinoma of the head and neck.

PubMed

Teknos, Theodoros N; Islam, Mozaffarul; Arenberg, Douglas A; Pan, Quintin; Carskadon, Shannon L; Abarbanell, Aaron M; Marcus, Benjamin; Paul, Supriti; Vandenberg, Curtis D; Carron, Michael; Nor, Jacques E; Merajver, Sofia D

2005-03-01

To assess the effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth rate in human squamous cell carcinoma (SCC). Three human SCC cell lines were used in this study for both in vitro and in vivo investigations. Conditioned media from untreated and tetrathiomolybdate-treated cell lines were compared with regard to cytokine levels, endothelial cell chemotaxis, endothelial cell tubule formation, and migration and the ability to induce angiogenesis in a rat aortic ring array. In vivo UM-SCC-38 was seeded onto tissue-engineered scaffolds and surgically implanted into the flanks of immunodeficient mice. Tumor growth rates and the level of angiogenesis were compared after 2 weeks of therapy. A tertiary care facility. In this study, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by head and neck SCC (HNSCC) cell lines in vitro. Furthermore, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by HNSCC cell lines in vitro. Furthermore, tetrathiomolybdate treatment of HNSCC cell lines results in significantly decreased endothelial cell chemotaxis, tubule formation, and neovascularization in a rat aortic ring assay. This in vitro evidence of decreased angiogenesis by tetrathiomolybdate is confirmed in vivo by using a severe combined immunodeficiency disorder mouse model in which tetrathiomolybdate therapy is shown to prevent human blood vessel formation. Finally, human HNSCC implanted into immunodeficient mice grow to a much larger size in untreated mice compared with those treated with 0.7 mL/kg per day of oral tetrathiomolybdate. These findings illustrate the ability of tetrathiomolybdate to down-regulate proinflammatory and proangiogenic cytokines in HNSCC. These observations are potentially exciting from a clinical perspective because a global decrease in these cytokines may decrease tumor aggressiveness and reverse the resistance to chemotherapy and radiation therapy seen in this tumor type.

Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism

PubMed Central

Carrillo-Sepúlveda, Maria Alícia; Ceravolo, Graziela S.; Furstenau, Cristina R.; Monteiro, Priscilla de Souza; Bruno-Fortes, Zuleica; Carvalho, Maria Helena; Laurindo, Francisco R.; Tostes, Rita C.; Webb, R. Clinton; Barreto-Chaves, Maria Luiza M.

2013-01-01

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 µmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium. PMID:23637941

Effects of agents that inactivate free radical NO (NO•) on nitroxyl anion-mediated relaxations, and on the detection of NO• released from the nitroxyl anion donor Angeli's salt

PubMed Central

Ellis, Anthie; Lu, Hong; Li, Chun Guang; Rand, Michael J

2001-01-01

The effects of agents that inactivate free radical nitric oxide (carboxy-PTIO, hydroxocobalamin and pyrogallol) were tested on relaxations produced by the nitroxyl anion (NO−) donor Angeli's salt in rat aortic rings and anococcygeus muscles. The amount of NO• generated from Angeli's salt in the presence of these agents was measured using a NO•-selective electrode sensor. Carboxy-PTIO (100, 300 μM), hydroxocobalamin (30, 100 μM) and pyrogallol (10, 30 μM) significantly reduced relaxations produced by Angeli's salt (0.3 μM) in aortic rings but not in anococcygeus muscles. NO• generated from Angeli's salt (0.1 – 10 μM), as detected by the sensor electrode, was less than 0.5% of the amount of Angeli's salt added. Carboxy-PTIO (100 μM) and hydroxocobalamin (30 μM), but not pyrogallol significantly increased the amount of NO• detected. In the presence of an oxidizing agent copper [II] (as CuSO4 100 μM), the amount of NO• detected from 0.3 μM of Angeli's salt increased from an undetectable level of 142.7±15.7 nM (equivalent to 47.6% of Angeli's salt added). Under these conditions, carboxy-PTIO, hydroxocobalamin and pyrogallol significantly reduced the amount of NO• detected from Angeli's salt as well as the signal generated by an equivalent amount of authentic NO (0.33 μM). The difference in effects of these agents on relaxations to Angeli's salt in the aorta and the anococcygeus muscle may be explained by the ready conversion of NO− to NO• in the aorta through an unidentified mechanism, which makes NO− susceptible to inactivation by these agents. Furthermore, in addition to inactivating NO•, carboxy-PTIO and hydroxocobalamin may themselves oxidize NO− to NO•, albeit slightly. PMID:11588105

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PubMed

Buzinari, Tereza Cristina; Oishi, Jorge Camargo; De Moraes, Thiago Francisco; Vatanabe, Izabela Pereira; Selistre-de-Araújo, Heloisa Sobreiro; Pestana, Cezar Rangel; Rodrigues, Gerson Jhonatan

2017-07-15

Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O 2 •- ) was obtained by using DHE probe. Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O 2 •- in HUVEC cells. The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats.

PubMed

Lim, Yee-Ling; Mok, Shiueh-Lian

2010-01-01

To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro. The antihypertensive activity of 11 species of seaweeds (5 brown, 1 red and 5 green algae) were tested by cumulative addition of the extracts to phenylephrine (PE)-precontracted Wistar-Kyoto (WKY) aortic rings in in vitro isometric contraction studies. Mechanisms for vasorelaxant effect were investigated in the presence of various antagonists. Of the 11 species tested, 2 showed a vasorelaxant effect. Further investigation of the mechanisms of action of the aqueous extract of green alga, Cladophora patentiramea (AECP),showed that the vascular relaxant effect was endothelium- and concentration-dependent. A maximum relaxation of 45.8 +/- 4.6% (n = 8, p < 0.001) was obtained at 0.1 mg/ml of extract, after which the response was found to reduce in a concentration-dependent manner to 15.7 +/- 4.9% (n = 8, p < 0.001) at the highest extract concentration tested. Pretreatment of endothelium-intact aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME, 30 microM), (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) and methylene blue (100 microM) resulted in a complete blockade of AECP-induced vasorelaxation. However, the relaxant effects of the extract were not blocked by atropine (1 microM), indomethacin (10 microM) and glibenclamide (10 microM), although the maximum relaxant responses were enhanced in the presence of glibenclamide. Our data showed that the in vitro vascular relaxant effect of AECPwas mediated through endothelium-dependent nitric oxide-cGMP pathway, and was not associated with the release of vasodilator prostaglandins, activation of muscarinic receptors, or ATP-sensitive potassium channels opening. Copyright 2010 S. Karger AG, Basel.

GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth factor receptor-dependent signalling pathway.

PubMed

Jang, Eun Jin; Seok, Young Mi; Arterburn, Jeffrey B; Olatunji, Lawrence A; Kim, In Kyeom

2013-10-01

The G protein-coupled oestrogen receptor-1 (GPER-1) agonist G1 induces endothelium-dependent relaxation. Activation of the epidermal growth factor (EGF) receptor leads to transduction of signals from the plasma membrane for the release of nitric oxide. We tested the hypothesis that G1 induces endothelium-dependent vasorelaxation through activation of the EGF receptor. Rat aortic rings were mounted in organ baths. After pretreatment with various inhibitors, aortic rings contracted with 11,9-epoxymethano-prostaglandin F2α or KCl were subjected to relaxation by G1. G1 induced endothelium-dependent vasorelaxation, which was attenuated by pretreatment with either L -N(ω) -nitroarginine methyl ester (L -NAME), an inhibitor of nitric oxide synthase, or (3aS,4R,9bR)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline HB-EGF, heparin-binding EGF-like growth factor, a GPER-1 antagonist. Neither a general oestrogen receptor antagonist, ICI 182 780, nor a selective oestrogen receptor-α antagonist, methyl-piperidino-pyrazole dihydrochloride (MPP), had an effect on G1-induced vasorelaxation. However, pretreatment with EGF receptor blockers, AG1478 or DAPH, resulted in attenuated G1-induced vasorelaxation. In addition, pretreatment with Src inhibitor 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine or Akt inhibitor VIII also resulted in attenuated vascular relaxation induced by the cumulative addition of G1. However, neither phosphatidylinositol-3 kinase inhibitors LY294002 and wortmannin nor an extracellular signal-regulated kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene monoethanolate had effect on vascular relaxation induced by the cumulative addition of G1. G1 induces endothelium-dependent vasorelaxation through Src-mediated activation of the EGF receptor and the Akt pathway in rat aorta. © 2013 Royal Pharmaceutical Society.

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

PubMed

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

Vascular protective actions of a nitric oxide aspirin analog in both in vitro and in vivo models of diabetes mellitus.

PubMed

Pieper, Galen M; Siebeneich, Wolfgang; Olds, Cara L; Felix, Christopher C; Del Soldato, Piero

2002-06-01

Defective endothelium-dependent relaxation is observed in experimental and human diabetes mellitus. The nature of this defect is not fully understood but may involve decreased nitric oxide (NO) bioactivity due to enhanced production of reactive oxygen species (ROS). In this paper, we examine the benefits and actions of a novel NO-donating, antioxidant called 2-acetoxybenzoic acid 2-(2-nitrooxymethyl) phenyl ester, and denoted as NCX4016, on NO-mediated endothelium-dependent relaxation in normal arteries exposed to acute elevations in glucose or in arteries derived from chronic diabetic animals. Intrinsic free radical scavenging by NO-NSAIDs in solution were evaluated using electron paramagnetic resonance (EPR) spectroscopy and spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In acute studies, normal rat aortas were exposed in tissue culture for 18 h to 5.5 mM or 40 mM in the presence or absence of NCX4016, a NO-donating NSAID unrelated to aspirin (NCX2216) or aspirin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined. For chronic hyperglycemia, diabetes was induced in rats by intravenous injection with streptozotocin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined after 8 wks in untreated animals or animals chronically-treated with NCX4016. Antioxidant efficacy in vivo was determined by measurement of plasma isoprostanes and by nuclear binding activity of NF-kappaB in nuclear fractions of aortae. Incubation with NCX4016 and NCX2216 produced a concentration-dependent inhibition of DMPO-OH formation indicating scavenging of hydroxyl radicals (HO(*)). In contrast, little efficacy to scavenge superoxide anion radicals was noted. Acute incubation of normal arteries with elevated glucose concentration caused inhibition of normal relaxation to acetylcholine. This impairment was prevented by co-incubation with NCX4106 but not by mannitol, the parent compound (aspirin) or by NCX2216. In addition, chronic treatment with NCX4016 prevented the development of defective endothelium-dependent relaxation to acetylcholine. This protection did not occur as a result to any changes in blood glucose concentration or hemoglobin glycation. Treatment with NCX4016 did decrease the elevation in plasma isoprostanes and normalized the diabetes-induced increase in NF-kappaB binding activity in nuclear fractions derived from aortic tissue. Collectively, these studies suggest that antioxidant interventions using NO-donating NSAIDs may provide an important novel therapeutic strategy to protect the diabetic endothelium.

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

PubMed

Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2015-06-01

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD(+) on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fibers) are probably related to activation of P1 and P2 purinoceptors.

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ClinicalTrials.gov

2018-02-19

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats.

PubMed

Nasri, Sima; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht; Rabani, Tahereh; Balvardi, Mahboubeh

2011-09-01

Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Male diabetic rats received C3G (10mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. III. Ventilation, respiratory monitoring, treatment for postoperative pain].

PubMed

Skarda, R T; Hubbell, J A; Muir, W W; Bednarski, R M; Mason, D E

1996-01-01

The purpose of this study was to review ventilation and postoperative analgesic technics in 137 dogs and 13 cats with congenital or acquired heart disease. The animals were referred to the Department of Veterinary Clinical Sciences at The Ohio State University, U.S.A, for the following surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch ring anomaly (3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). Controlled ventilation was used in all animals during thoracotomy. Anesthesia was maintained over 2.3 +/- 1.3 hours by using either isoflurane, halothane, propofol, or diazepam-ketamine in 64%, 32%, 2%, and 0.7% of animals, respectively. Postoperative analgesia was necessary in 20% of animals and was provided by using different technics over several hours. The technics and respective percentages of animals in which they were used, were: intravenous buprenorphine (3.3%), intercostal nerve blocks (8.7%), epidural morphine (4%), and interpleural regional analgesia (4%).

Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic

PubMed Central

Oskowitz, Adam; McFerrin, Harris; Gutschow, Miriam; Carter, Mary Leita; Pochampally, Radhika

2016-01-01

Recent reports have indicated that mesenchymal stromal cells (MSCs) from bone marrow have a potential in vascular remodeling and angiogenesis. Here, we report a unique phenomenon that under serum-deprived conditions MSCs survive and replicate. Secretome analysis of MSCs grown under serum-deprived conditions (SD-MSCs) identified a significant upregulation of prosurvival and angiogenic factors including VEGF-A, ANGPTs, IGF-1, and HGF. An ex vivo rat aortic assay demonstrated longer neovascular sprouts generated from rat aortic rings cultured in SD-MSC-conditioned media compared to neovascular sprouts from aortas grown in MSC-conditioned media. With prolonged serum deprivation, a subpopulation of SD-MSCs began to exhibit an endothelial phenotype. This population expressed endothelial-specific proteins including VEGFR2, Tie2/TEK, PECAM/CD31, and eNOS and also demonstrated the ability to uptake acetylated LDL. SD-MSCs also exhibited enhanced microtubule formation in an in vitro angiogenesis assay. Modified chick chorioallantoic membrane (CAM) angiogenesis assays showed significantly higher angiogenic potential for SD-MSCs compared to MSCs. Analysis of CAMs grown with SD-MSCs identified human-specific CD31-positive cells in vascular structures. We conclude that under the stress of serum deprivation MSCs are highly angiogenic and a population of these cells has the potential to differentiate into endothelial-like cells. PMID:21421339

Outcomes of ring versus suture annuloplasty for tricuspid valve repair in patients undergoing mitral valve surgery.

PubMed

Shinn, Sung Ho; Dayan, Victor; Schaff, Hartzell V; Dearani, Joseph A; Joyce, Lyle D; Lahr, Brian; Greason, Kevin L; Stulak, John M; Daly, Richard C

2016-08-01

There is controversy regarding the comparative effectiveness of methods of tricuspid valve (TV) repair-prosthetic ring versus suture annuloplasty-in patients undergoing operation for primary mitral valve (MV) disease. In this study, we analyzed factors associated with patient survival and recurrent tricuspid regurgitation (TR) following TV repair and focused on results stratified by method of tricuspid valve repair. We reviewed patients who underwent TV repair with suture (De Vega) or flexible ring annuloplasties at the time of MV surgery from 1995 to 2010. Patients with prior cardiac or concomitant aortic valve operations were excluded. Propensity matching was performed to account for potential differences in baseline characteristics between the groups. Primary outcomes were long-term mortality and postoperative TR grade. In the overall study, there were 415 patients with median age 72 years (range, 63-78 years), from which 148 matched pairs were identified by propensity score analysis. In the overall cohort, patients in the ring annuloplasty group more often had preoperative transvenous pacemakers (P = .05), lower ejection fractions (P = .028), and more recent years of operation (P < .001). For patients who had De Vega suture annuloplasty, long-term mortality was not different from that of patients who had ring annuloplasty (hazard ratio, 0.93; 95% confidence interval, 0.67-1.30). Older age, preoperative diabetes, and preoperative right ventricular dysfunction were predictors for long-term mortality. Durability of the annuloplasty methods was similar with no significant difference in trend of recurrent TR grades over follow-up (P = .807). Etiology of mitral regurgitation was not associated with recurrent TR during follow-up (P = .857). Late survival and TV durability following concomitant TV repair during MV surgery did not differ with respect to TV repair technique. In this series of patients with repaired tricuspid valves, etiology of MV disease did not influence postoperative changes in TR. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans.

PubMed

Buonsanti, M Federica; Bertinaria, Massimo; Stilo, Antonella Di; Cena, Clara; Fruttero, Roberta; Gasco, Alberto

2007-10-04

The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution to trachea relaxation was evident with product 15b at micromolar concentrations. All the new NO-donor hybrids were able to dilate rat aortic strips precontracted with phenylephrine. Both furoxan and furazan derivatives displayed antioxidant activity greater than that of fenoterol.

Inhibitor of prostacyclin production in sporadic haemolytic uraemic syndrome.

PubMed Central

Levin, M; Elkon, K B; Nokes, T J; Buckle, A M; Dillon, M J; Hardisty, R M; Barratt, T M

1983-01-01

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors. PMID:6354101

Aortic valve dysfunction and aortic dilation in adults with coarctation of the aorta.

PubMed

Clair, Mathieu; Fernandes, Susan M; Khairy, Paul; Graham, Dionne A; Krieger, Eric V; Opotowsky, Alexander R; Singh, Michael N; Colan, Steven D; Meijboom, Erik J; Landzberg, Michael J

2014-01-01

To determine the prevalence of aortic valve dysfunction, aortic dilation, and aortic valve and ascending aortic intervention in adults with coarctation of the aorta (CoA). Aortic valve dysfunction and aortic dilation are rare among children and adolescents with CoA. With longer follow-up, adults may be more likely to have progressive disease. We retrospectively reviewed all adults with CoA, repaired or unrepaired, seen at our center between 2004 and 2010. Two hundred sixteen adults (56.0% male) with CoA were identified. Median age at last evaluation was 28.3 (range 18.0 to 75.3) years. Bicuspid aortic valve (BAV) was present in 65.7%. At last follow-up, 3.2% had moderate or severe aortic stenosis, and 3.7% had moderate or severe aortic regurgitation. Dilation of the aortic root or ascending aorta was present in 28.0% and 41.6% of patients, respectively. Moderate or severe aortic root or ascending aortic dilation (z-score > 4) was present in 8.2% and 13.7%, respectively. Patients with BAV were more likely to have moderate or severe ascending aortic dilation compared with those without BAV (19.5% vs. 0%; P < 0.001). Age was associated with ascending aortic dilation (P = 0.04). At most recent follow-up, 5.6% had undergone aortic valve intervention, and 3.2% had aortic root or ascending aortic replacement. In adults with CoA, significant aortic valve dysfunction and interventions during early adulthood were uncommon. However, aortic dilation was prevalent, especially of the ascending aorta, in patients with BAV. © 2013 Wiley Periodicals, Inc.

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Eatman, D.; Listhrop, R. A.; Beasley, A. S.; Socci, R. R.; Abukhalaf, I.; Bayorh, M. A.

2003-01-01

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside

PubMed Central

Saxon, John T; Allen, Keith B; Cohen, David J

2018-01-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient–prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient–prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions. PMID:29593832

Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation

PubMed Central

Valente, Acrisio Sales; Alencar, Polyanna; Santos, Alana Neiva; Lobo, Roberto Augusto de Mesquita; de Mesquita, Fernando Antônio; Guimarães, Aloyra Guedis

2013-01-01

The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course. PMID:24598962

Toxicology and pharmacology of some ruthenium compounds: Vascular smooth muscle relaxation by nitrosyl derivatives of ruthenium and iridium.

PubMed

Kruszyna, H; Kruszyna, R; Hurst, J; Smith, R P

1980-07-01

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55;dichlorobis(2,2'-dipyridyl)ruthenium(II), 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occurring in 4-7d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be due to the metal and not to its associated ligands. Only complexes having nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic agonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominus when these isolated muscles had been contracted by acetylcho line. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimally lethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.

Minimally Invasive Aortic Valve Replacement Following Root Enlargement on too Narrow Annulus to Perform Transcatheter Aortic Valve Implantation.

PubMed

Sakamoto, Kosuke; Totsugawa, Toshinori; Hiraoka, Arudo; Tamura, Kentaro; Yoshitaka, Hidenori; Sakaguchi, Taichi

2018-05-30

An 88-year-old woman was diagnosed with aortic stenosis and an aortic annulus that was too narrow to perform transcatheter aortic valve implantation. Surgery was performed through a 7-cm right mini-thoracotomy at the fourth intercostal space. A 19-mm aortic valve bioprosthesis was implanted after root enlargement. The fourth intercostal space was a suitable site for aortic root enlargement because of the shorter skin-to-root distance and the detailed exposure of the aortic valve after cutting the aortic wall. This study concluded that minimally-invasive aortic valve replacement following root enlargement can be an option for the treatment of elderly patients with aortic stenosis accompanied by an annulus that is too small to perform transcatheter aortic valve implantation.

Bicuspid Aortic Valve

DTIC Science & Technology

2006-08-01

severe aortic stenosis . Figure 1F. Oblique axial cine bright blood imaging through the valve plane of the aorta, demonstrates the aortic valve to...the ascending aorta. This moderate to large jet is consistent with moderate to severe aortic stenosis . No diastolic jet to suggest aortic ...conditions. Functional impairment of the aortic valve—namely aortic stenosis and aortic regurgitation—is the most common complication (in up to 68-85% of

Bicuspid aortic valves: diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT.

PubMed

Murphy, David J; McEvoy, Sinead H; Iyengar, Sri; Feuchtner, Gudrun; Cury, Ricardo C; Roobottom, Carl; Baumueller, Stephan; Alkadhi, Hatem; Dodd, Jonathan D

2014-08-01

To assess the diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT for bicuspid aortic valves. The standard axial chest CT scans of 20 patients with known bicuspid aortic valves were blindly, randomly analyzed for (i) the appearance of the valve cusps, (ii) the largest aortic sinus area, (iii) the longest aortic cusp length, (iv) the thickest aortic valve cusp and (v) valve calcification. A second blinded reader independently analyzed the appearance of the valve cusps. Forty-two age- and sex-matched patients with known tricuspid aortic valves were used as controls. Retrospectively ECG-gated cardiac CT multiphase reconstructions of the aortic valve were used as the gold-standard. Fourteen (21%) scans were scored as unevaluable (7 bicuspid, 7 tricuspid). Of the remainder, there were 13 evaluable bicuspid valves, ten of which showed an aortic valve line sign, while the remaining three showed a normal Mercedes-Benz appearance owing to fused valve cusps. The 35 evaluable tricuspid aortic valves all showed a normal Mercedes-Benz appearance (P=0.001). Kappa analysis=0.62 indicating good interobserver agreement for the aortic valve cusp appearance. Aortic sinus areas, aortic cusp lengths and aortic cusp thicknesses of ≥ 3.8 cm(2), 3.2 cm and 1.6mm respectively on standard axial chest CT best distinguished bicuspid from tricuspid aortic valves (P<0.0001 for all). Of evaluable scans, the sensitivity, specificity, positive and negative predictive values of standard axial chest CT in diagnosing bicuspid aortic valves was 77% (CI 0.54-1.0), 100%, 100% and 70% respectively. The aortic valve is evaluable in approximately 80% of standard chest 64-slice CT scans. Bicuspid aortic valves may be diagnosed on evaluable scans with good diagnostic accuracy. An aortic valve line sign, enlarged aortic sinuses and elongated, thickened valve cusps are specific CT features. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Spectrum of Aortic Valve Abnormalities Associated with Aortic Dilation Across Age Groups in Turner Syndrome

PubMed Central

Olivieri, Laura J.; Baba, Ridhwan Y.; Arai, Andrew E.; Bandettini, W. Patricia; Rosing, Douglas R.; Bakalov, Vladimir; Sachdev, Vandana; Bondy, Carolyn A.

2014-01-01

Background Congenital aortic valve fusion is associated with aortic dilation, aneurysm and rupture in girls and women with Turner syndrome (TS). Our objective was to characterize aortic valve structure in subjects with TS, and determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results The aortic valve and thoracic aorta were characterized by cardiovascular magnetic resonance imaging in 208 subjects with TS in an IRB-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve, and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve (TAV) 64%(n=133), partially fused aortic valve (PF) 12%(n=25), bicuspid aortic valve (BAV) 23%(n=47), and unicuspid aortic valve (UAV) 1%(n=3). Age and body surface area (BSA) were similar in the 4 valve morphology groups. There was a significant trend, independent of age, towards larger BSA-indexed ascending aortic diameters (AADi) with increasing valve fusion. AADi were (mean +/− SD) 16.9 +/− 3.3 mm/m2, 18.3 +/− 3.3 mm/m2, and 19.8 +/− 3.9 mm/m2 (p<0.0001) for TAV, PF and BAV+UAV respectively. PF, BAV, and UAV were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Conclusions Aortic valve abnormalities in TS occur with a spectrum of severity, and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased AADi. PMID:24084490

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.

1986-05-01

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM (/sup 14/C)GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentrationmore » was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM (/sup 14/C)GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST« less

Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI.

PubMed

Qi, Chun-Mei; Du, Lili; Wu, Wei-Heng; Li, Dong-Ye; Hao, Ji; Gong, Lei; Deng, Liangrong; Zhang, Tao; Zhang, Chao; Zhang, Yu

2015-11-01

This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper venom and histamine. Pre-contrast images and USPIO-enhanced MRI images were obtained after pharmacological triggering with injection of USPIO for 5 days. Blood specimens were taken for biochemical and serological tests at 0 and 18 weeks. Abdominal aorta was histologically studied. The levels of serum ICAM-1 and VCAM-1 were quantified by ELISA. Vulnerable plaques appeared as a local hypo-intense signal on the USPIO-enhanced MRI, especially on T2*-weighted sequences. The signal strength of plaques reached the peak at 96 h. Lipid levels were significantly (p < 0.05) higher in both Group A and B compared with the levels before the high cholesterol diet. The ICAM-1 and VCAM-1 levels were significantly (p < 0.05) higher in Group B compared with Group A. The USPIO-enhanced MRI efficiently identifies vulnerable plaques due to accumulation of USPIO within macrophages in abdominal aorta plaques.

SR high-speed K-edge subtraction angiography in the small animal (abstract)

NASA Astrophysics Data System (ADS)

Takeda, T.; Akisada, M.; Nakajima, T.; Anno, I.; Ueda, K.; Umetani, K.; Yamaguchi, C.

1989-07-01

To assess the ability of the high-speed K-edge energy subtraction system which was made at beamline 8C of Photon Factory, Tsukuba, we performed an animal experiment. Rabbits were used for the intravenous K-edge subtraction angiography. In this paper, the actual images of the artery obtained by this system, are demonstrated. The high-speed K-edge subtraction system consisted of movable silicon (111) monocrystals, II-ITV, and digital memory system. Image processing was performed by 68000-IP computer. The monochromatic x-ray beam size was 50×60 mm. Photon energy above and below iodine K edge was changed within 16 ms and 32 frames of images were obtained sequentially. The rabbits were anaesthetized by phenobarbital and a 5F catheter was inserted into inferior vena cava via the femoral vein. 1.5 ml/kg of contrast material (Conlaxin H) was injected at the rate of 0.5 ml/kg/s. TV images were obtained 3 s after the starting point of injection. By using this system, the clear K-edge subtracted images were obtained sequentially as a conventional DSA system. The quality of the images were better than that obtained by DSA. The dynamical blood flow was analyzed, and the best arterial image could be selected from the sequential images. The structures of aortic arch, common carotid arteries, right subclavian artery, and internal thoracic artery were obtained at the chest. Both common carotid arteries and vertebral arteries were recorded at the neck. The diameter of about 0.3-0.4 mm artery could be clearly revealed. The high-speed K-edge subtraction system demonstrates the very sharp arterial images clearly and dynamically.

Deep sea water modulates blood pressure and exhibits hypolipidemic effects via the AMPK-ACC pathway: an in vivo study.

PubMed

Sheu, Ming-Jyh; Chou, Pei-Yu; Lin, Wen-Hsin; Pan, Chun-Hsu; Chien, Yi-Chung; Chung, Yun-Lung; Liu, Fon-Chang; Wu, Chieh-Hsi

2013-06-17

Deep sea water (DSW), originally pumped from the Pacific Rim off the coast of Hualien County (Taiwan), and its mineral constituents, were concentrated by a low-temperature vacuum evaporation system to produce a hardness of approximately 400,000 mg/L of seawater mineral concentrate. The primary composition of this seawater mineral concentrate was ionic magnesium (Mg²⁺), which was approximately 96,000 mg/L. Referring to the human recommended daily allowance (RDA) of magnesium, we diluted the mineral concentrate to three different dosages: 0.1 × DSW (equivalent to 3.75 mg Mg²⁺/kg DSW); 1 × DSW (equivalent to 37.5 mg Mg²⁺/kg DSW); and 2 × DSW (equivalent to 75 mg Mg²⁺/kg DSW). Additionally, a magnesium chloride treatment was conducted for comparison with the DSW supplement. The study indicated that 0.1 × DSW, 1 × DSW and 2 × DSW decreased the systolic and diastolic pressures in spontaneous hypertensive rats in an eight-week experiment. DSW has been shown to reduce serum lipids and prevent atherogenesis in a hypercholesterolemic rabbit model. Our results demonstrated that 1 × DSW and 2 × DSW significantly suppressed the serum cholesterol levels, reduced the lipid accumulation in liver tissues, and limited aortic fatty streaks. These findings indicated that the antiatherogenic effects of DSW are associated with 5'-adenosine monophosphate-activated protein kinase (AMPK) stimulation and the consequent inhibition of phosphorylation of acetyl-CoA carboxylase (ACC) in atherosclerotic rabbits. We hypothesize that DSW could potentially be used as drinking water because it modulates blood pressure, reduces lipids, and prevents atherogenesis.

The Aachen miniaturized heart-lung machine--first results in a small animal model.

PubMed

Schnoering, Heike; Arens, Jutta; Sachweh, Joerg S; Veerman, Melanie; Tolba, Rene; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Vazquez-Jimenez, Jaime F

2009-11-01

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth-weight newborns. Taking these considerations into account, the Aachen miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross-clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O(2) and CO(2)) may reduce circuit-induced complications during heart surgery in neonates.

Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders: Relationships With Age, Aortic Size, Rate of Dilation, and Surgical Root Replacement.

PubMed

Prakash, Ashwin; Adlakha, Himanshu; Rabideau, Nicole; Hass, Cara J; Morris, Shaine A; Geva, Tal; Gauvreau, Kimberlee; Singh, Michael N; Lacro, Ronald V

2015-08-18

Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs. Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and β-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter z score per year. In 83 CTD patients (median age, 24 years; range, 1-55; 17% <18 years of age; 60% male), ascending aorta distensibility was reduced in comparison with published normative values: median z score, -1.93 (range, -8.7 to 1.3; P<0.0001 versus normals). Over a median follow-up period of 2.7 years, there were no aortic dissections or deaths, but 16 of 83 (19%) patients underwent surgical aortic root replacement. In multivariable analysis, lower aortic root strain (P=0.05) and higher vertebral tortuosity index (P=0.01) were independently associated with aortic root replacement. Lower ascending aorta strain (P=0.02) was associated with a higher rate of aortic root dilation. Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs. © 2015 American Heart Association, Inc.

Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis

PubMed Central

Dilu, VP; George, Raju

2017-01-01

Introduction An integrated approach that incorporates two dimensional, M mode and Doppler echocardiographic evaluation has become the standard means for accurate quantification of severity of valvular aortic stenosis. Maximal separation of the aortic valve cusps during systole has been shown to correlate well with the severity of aortic stenosis measured by other echocardiographic parameters. Aim To study the correlation between Maximal Aortic valve Cusp Separation (MACS) and severity of aortic valve stenosis and to find cut-off values of MACS for detecting severe and mild aortic stenosis. Materials and Methods In the present prospective observational study, we have compared the accuracy of MACS distance and the aortic valve area calculated by continuity equation in 59 patients with varying degrees of aortic valve stenosis. Aortic leaflet separation in M mode was identified as the distance between the inner edges of the tips of these structures at mid systole in the parasternal long axis view. Cuspal separation was also measured in 2D echocardiography from the parasternal long axis view and the average of the two values was taken as the MACS. Patients were grouped into mild, moderate and severe aortic stenosis based on the aortic valve area calculated by continuity equation. The resultant data regarding maximal leaflet separation on cross-sectional echocardiogram was then subjected to linear regression analysis in regard to correlation with the peak transvalvular aortic gradient as well as the calculated aortic valve area. A cut-off value for each group was derived using ROC curve. Results There was a strong correlation between MACS and aortic valve area measured by continuity equation and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis, with high sensitivity, specificity and positive predictive value. MACS above 11.25 mm practically ruled out significant aortic stenosis. Conclusion Measurement of MACS is a simple echocardio-graphic method to assess the severity of valvular aortic stenosis, with high sensitivity and specificity. MACS can be extremely useful in two clinical situations as a simple screening tool for assessment of stenosis severity and also helps in decision making non invasively when there is discordance between the other echocardiographic parameters of severity of aortic stenosis. PMID:28764221

Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation

PubMed Central

Spina, Roberto; Anthony, Chris; Muller, David WM

2015-01-01

Transcatheter aortic valve replacement with either the balloon-expandable Edwards SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the established therapeutic modality for severe aortic valve stenosis in patients who are not deemed suitable for surgical intervention due to excessively high operative risk. Native aortic valve regurgitation, defined as primary aortic incompetence not associated with aortic stenosis or failed valve replacement, on the other hand, is still considered a relative contraindication for transcatheter aortic valve therapies, because of the absence of annular or leaflet calcification required for secure anchoring of the transcatheter heart valve. In addition, severe aortic regurgitation often coexists with aortic root or ascending aorta dilatation, the treatment of which mandates operative intervention. For these reasons, transcatheter aortic valve replacement has been only sporadically used to treat pure aortic incompetence, typically on a compassionate basis and in surgically inoperable patients. More recently, however, transcatheter aortic valve replacement for native aortic valve regurgitation has been trialled with newer-generation heart valves, with encouraging results, and new ancillary devices have emerged that are designed to stabilize the annulus–root complex. In this paper we review the clinical context, technical characteristics and outcomes associated with transcatheter treatment of native aortic valve regurgitation. PMID:29588674

Durability of central aortic valve closure in patients with continuous flow left ventricular assist devices.

PubMed

McKellar, Stephen H; Deo, Salil; Daly, Richard C; Durham, Lucian A; Joyce, Lyle D; Stulak, John M; Park, Soon J

2014-01-01

A competent aortic valve is essential to providing effective left ventricular assist device support. We have adopted a practice of central aortic valve closure by placing a simple coaptation stitch at left ventricular assist device implantation in patients with significant aortic insufficiency. We conducted a follow-up study to evaluate the efficacy and durability of this procedure. The study included patients who had undergone continuous flow left ventricular assist device implantation. The patients were divided into 2 groups, those who did not require any aortic procedure because the valve was competent and those who underwent central aortic valve closure for mild or greater aortic regurgitation. The clinical endpoints were mortality, progression or recurrence of aortic insufficiency, and reoperation for aortic valve pathologic features. Aortic insufficiency was measured qualitatively from mild to severe on a scale of 0 to 5. A total of 123 patients received continuous flow left ventricular assist devices from February 2007 to August 2011. Of those, 18 (15%) underwent central aortic valve closure at left ventricular assist device implantation because of significant aortic insufficiency (1.8 ± 1.4) and 105 who did not (competent aortic valve, 0.15 ± 0.43; P < .01). At follow-up (median, 312 days; range, 0-1429 days), the mean aortic insufficiency score remained low for the patients with central aortic valve closure (0.27 ± 0.46) in contrast to those without central aortic valve closure who experienced aortic insufficiency progression (0.78 ± 0.89; P = .02). In addition, the proportion of patients with more than mild aortic insufficiency was significantly less in the central aortic valve closure group (0% vs 18%; P = .05). The patients in the central aortic valve closure group were significantly older and had a greater incidence of renal failure at baseline. The 30-day mortality was greater in the central aortic valve closure group, but the late survival was similar between the 2 groups. No reoperations were required for recurrent aortic insufficiency. The results of our study have shown that repair of aortic insufficiency with a simple central coaptation stitch is effective and durable in left ventricular assist device-supported patients, with follow-up extending into 2 years. Although aortic insufficiency progressed over time in those with minimal native valve regurgitation initially, no such progression was noted in those with central aortic valve closure. Additional investigation is needed to evaluate whether prophylactic central aortic valve closure should be performed at left ventricular assist device implantation to avoid problematic aortic regurgitation developing over time, in particular in patients undergoing left ventricular assist device implantation for life-long (destination therapy) support. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement.

PubMed

Polimenakos, Anastasios C; Sathanandam, Shyam; Elzein, Chawki; Barth, Mary J; Higgins, Robert S D; Ilbawi, Michel N

2010-04-01

Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. There were no early, intermediate, or late deaths. Z-values of left ventricular end-diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Pulse Wave Analysis after Treatment of Abdominal Aortic Aneurysms with the Ovation Device.

PubMed

Georgakarakos, Efstratios; Argyriou, Christos; Georgiadis, George S; Lazarides, Miltos K

2017-04-01

Ovation aortic stent-graft system is a new device for the endovascular treatment of Abdominal Aortic Aneurysms achieving fixation via a 35-mm long, rigid anchored suprarenal stent and sealing stent at the infrarenal level by a means of a polymer-filling pair of inflatable O-rings, which cause narrowing of flow lumen and regional stenosis. Thus, concerns have been raised regarding hemodynamic consequences associated with this new design. Our preliminary report showed no significant increase of aortic pulse wave velocity (aPWV) immediately after implantation of the ovation in 3 patients. We studied further the hemodynamic implications of the Ovation implantation in 6 patients for a follow-up of 6 months. A brachial cuff-based automatic oscillometric device (Mobil-O-Graph; IEM, Stolberg, Germany) was used to perform noninvasively pulse wave analysis and stiffness estimation. Measurements were held preoperatively in 6 patients treated for abdominal aortic aneurysm, at the end of the first postoperative week, first and sixth postoperative month. Changes in systolic and diastolic blood pressure (cSyst, cDiast), heart rate, aPWV, augmentation index (AI@75), augmentation pressure (AP), and in the amplitude ratio of the reflected-to-forward pressure waves (reflection magnitude, RM) were recorded and compared. Significant change in any parameter was examined via analysis of variance repeated measures. The cSyst was 132 ± 19.6, 127 ± 17.63, 131.3 ± 19.96, and 129.83 ± 31.72 mm Hg (P = 0.81) and cDiast was 88 ± 10.58, 86.83 ± 11.72, 89.83 ± 16.01, and 98.5 ± 24.56 mm Hg (P = 0.40). The heart rate showed an increasing yet nonsignificant tendency (67 ± 10.60, 75.1 ± 8.63, 74.33 ± 8.89, and 70.66 ± 6.65 beats/min, 0.27). The aPWV remained constant (11.61 ± 1.88, 11.6 ± 1.74, 11.8 ± 2.08, and 11.85 ± 2.30 m/sec, P = 0.79). Similarly, RM (71.16 ± 9.94, 60.66 ± 11.79, 61.5 ± 14.47, and 64.5 ± 3.78), AI@75 (33.83 ± 12.25, 22.16 ± 7.93, 27.83 ± 11.23, and 19.5 ± 14.72), and AP (18.33 ± 10.36, 9.83 ± 4.91, 11.5 ± 9.22, and 12 ± 15.08 mm Hg) remained practically unaltered during the follow-up period (P value: 0.79, 0.25, 0.10, and 0.27), respectively. The implantation of the Ovation stent graft does not cause increase in aortic stiffness or in pulse wave reflection in the mid-period. The rationale of investigating noninvasively the impact of aortic stent grafts on the mechanical properties and the hemodynamic parameters should be encouraged because such findings may contribute to further development of newer endograft designs. Copyright © 2016 Elsevier Inc. All rights reserved.

Study of the in vivo and in vitro cardiovascular effects of a hydralazine-like vasodilator agent (HPS-10) in normotensive rats

PubMed Central

Orallo, Francisco

1997-01-01

In this work, the cardiovascular effects of HPS-10, a new vasodilator agent, were studied in rats. In conscious normotensive rats, oral administration of HPS-10 (4–9 mg kg−1) produced a dose-related and long-lasting fall in systolic arterial blood pressure (ED30 of 5.32 mg kg−1), accompanied by an increase in heart rate (ED30 of 8.43 mg kg−1). This tachycardia was totally inhibited by pretreatment with (±)-propranolol (10 mg kg−1, p.o.). In anaesthetized normotensive rats, HPS-10 (0.3–0.6 mg kg−1, i.v.) produced a gradual, dose-dependent and sustained decrease in systolic, diastolic and mean arterial pressure (MAP) (ED30 for MAP of 0.41 mg kg−1, i.v.), accompanied by a significant bradycardia at high doses (>0.4 mg kg−1; ED20 of 0.61 mg kg−1, i.v.). HPS-10 (0.5 mg kg−1, i.v.) did not modify the positive chronotropic effects induced by intravenous administration of noradrenaline (NA; 5 μg kg−1), angiotensin II (AII; 0.2 μg kg−1) and nicotine (200 μg kg−1) but markedly inhibited the hypertensive response produced by these agents. In rat isolated rubbed aorta, HPS-10 (0.1–1 mM) non-competitively and with almost equal effectiveness antagonized the contractions induced by NA, AII (in normal Krebs solution) and Ca2+ (in depolarizing Ca2+-free high-K+ 50 mM solution). In the experiments in Ca2+-free medium, HPS-10 (1 mM) considerably inhibited the contractions induced by NA, AII and caffeine in rat aorta. Furthermore, in the studies with radioactive Ca2+, HPS-10 (1 mM) did not modify the basal uptake of 45Ca2+ but strongly decreased the influx of 45Ca2+ induced by NA, AII and K+ in rat aortic rings. In rat isolated atria, HPS-10 (1 mM) produced a positive inotropic/negative chronotropic effect. HPS-10 (0.3 mM) significantly inhibited the sustained and transient Ba2+ inward current (IBa) recorded in whole-cell clamped rat aortic myocytes. These results indicate that the non-selective vasorelaxant effects of HPS-10 in rat aortic rings can be attributed to transmembrane Ca2+-antagonist activity and an intracellular action on smooth muscle cells. The direct vasodilator action of HPS-10 observed in rat isolated aorta may be responsible for the HPS-10 hypotensive activity in anaesthetized normotensive rats. PMID:9283696

Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhirong; Chen Yan; Labinskyy, Nazar

Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression ofmore » tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol.« less

Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

PubMed

Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

2018-06-01

Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive disease and small abdominal aortic aneurysm separately.

Shape of the dilated aorta in children with bicuspid aortic valve

PubMed Central

Mart, Christopher R; McNerny, Bryn E

2013-01-01

Background: The dilated aorta in adults with bicuspid aortic valve has been shown to have different shapes, but it is not known if this occurs in children. This observational study was performed to determine if there are different shapes of the dilated aorta in children with bicuspid aortic valve and their association with age, gender, hemodynamic alterations, and degree of aortic enlargement. Methods: One hundred and eighty-seven echocardiograms done on pediatric patients (0 – 18 years) for bicuspid aortic valve, during 2008, were reviewed. Aortic valve morphology, shape/size of the aorta, and pertinent hemodynamic alterations were documented. Aortic dilation was felt to be present when at least one aortic segment had a z-score > 2.0; global aortic enlargement was determined by summing the aortic segment z-scores. The aortic shape was assessed by age, gender, valve morphology, and hemodynamic alterations. Results: Aortic dilation was present in 104/187 patients. The aorta had six different shapes designated from S1 through S6. There was no association between the aortic shape and gender, aortic valve morphology, or hemodynamic abnormalities. S3 was the most common after the age of six years and was associated with the most significant degree of global aortic enlargement. Conclusions: The shape of the dilated aorta in children with bicuspid aortic valve does not occur in a uniform manner and multiple shapes are seen. S2 and S3 are most commonly seen. As aortic dilation becomes more significant, a single shape (S3) becomes the dominant pattern. PMID:24688228

Landmark lecture: Perloff lecture: Tribute to Professor Joseph Kayle Perloff and lessons learned from him: aortopathy in adults with CHD.

PubMed

Niwa, Koichiro

2017-12-01

Marfan syndrome, bicuspid aortic valve, and/or coarctation of the aorta are associated with medial abnormalities of the ascending aortic or para-coarctation aorta. Medial abnormalities in the ascending aorta are prevalent in other type of patients with a variety of CHDs such as single ventricle, persistent truncus arteriosus, transposition of the great arteries, hypoplastic left heart syndrome, and tetralogy of Fallot, encompassing a wide age range and may predispose to dilatation, aneurysm, and rapture necessitating aortic valve and root surgery. These CHDs exhibit ongoing dilatation of the aortic root and reduced aortic elasticity and increased aortic stiffness that may relate to intrinsic properties of the aortic root. These aortic dilatation and increased stiffness can induce aortic aneurysm, rapture of the aorta, and aortic regurgitation, but also provoke left ventricular hypertrophy, reduced coronary artery flow, and left ventricular failure. Therefore, a new clinical entity can be used to call this association of aortic pathophysiological abnormality, aortic dilation, and aorto-left ventricular interaction - "aortopathy".

Aortic operation after previous coronary artery bypass grafting: management of patent grafts for myocardial protection.

PubMed

Nakajima, Masato; Tsuchiya, Koji; Fukuda, Shoji; Morimoto, Hironobu; Mitsumori, Yoshitaka; Kato, Kaori

2006-04-01

Aortic surgery for progressive aortic valve disease or aortic aneurysm after previous coronary artery bypass grafting (CABG) is a challenging procedure. We report the outcome of aortic reoperation after previous CABG and evaluate our management of patent grafts and our methods for obtaining myocardial protection. From February 2001 to July 2003, 6 patients with progressive aortic valve disease and aneurysm of the thoracic aorta were operated on. The group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4 patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic dissection, and 1 with progressive aortic valve stenosis. The interval between previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were performed via median resternotomy. Myocardial protection was obtained by hypothermic perfusion of patent in-situ arterial grafts following cold-blood cardioplegia administration via the aortic root under aortic cross clamping. The operative procedure was aortic arch replacement in 4 patients, ascending aortic replacement with double CABG in 1, and aortic valve replacement in 1. All patients survived the reoperation. Postoperative maximum creatine kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram nor were any new wall motion abnormalities recognized on echocardiography. There were no late deaths during a follow-up of 30.7 months. Reoperative aortic procedures after CABG can be performed safely with myocardial protection via hypothermic perfusion of a patent in-situ arterial graft.

Radiation exposure to eye lens and operator hands during endovascular procedures in hybrid operating rooms.

PubMed

Attigah, Nicolas; Oikonomou, Kyriakos; Hinz, Ulf; Knoch, Thomas; Demirel, Serdar; Verhoeven, Eric; Böckler, Dittmar

2016-01-01

The purpose of this study was to evaluate the radiation exposure of vascular surgeons' eye lens and fingers during complex endovascular procedures in modern hybrid operating rooms. Prospective, nonrandomized multicenter study design. One hundred seventy-one consecutive patients (138 male; median age, 72.5 years [interquartile range, 65-77 years]) underwent an endovascular procedure in a hybrid operating room between March 2012 and July 2013 in two vascular centers. The dose-area product (DAP), fluoroscopy time, operating time, and amount of contrast dye were registered prospectively. For radiation dose recordings, single-use dosimeters were attached at eye level and to the ring finger of the hand next to the radiation field of the operator for each endovascular procedure. Dose recordings were evaluated by an independent institution. Before the study, precursory investigations were obtained to simulate the radiation dose to eye lens and fingers with an Alderson phantome (RSD, Long Beach, Calif). Interventions were classified into six treatment categories: endovascular repair of infrarenal abdominal aneurysm (n = 65), thoracic endovascular aortic repair (n = 32), branched endovascular aortic repair for thoracoabdominal aneurysms (n = 17), fenestrated endovascular aortic repair for complex abdominal aortic aneurysm, (n = 25), iliac branched device (n = 8), and peripheral interventions (n = 24). There was a significant correlation in DAP between both lens (P < .01; r = 0.55) and finger (P < .01; r = 0.56) doses. The estimated fluoroscopy time to reach a radiation threshold of 20 mSv/y was 1404.10 minutes (90% confidence limit, 1160, 1650 minutes). According to correlation of the lens dose with the DAP an estimated cumulative DAP of 932,000 mGy/m(2) (90% confidence limit, 822,000, 1,039,000) would be critical for a threshold of 20 mSv/y for the eyes. Radiation protection is a serious issue for vascular surgeons because most complex endovascular procedures are delivering measurable radiation to the eyes. With the correlation of the DAP obtained in standard endovascular procedures a critical threshold of 20 mSv/y to the eyes can be predicted and thus an estimate of a potential harmful exposure to the eyes can be obtained. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Decreased expression of fibulin-4 in aortic wall of aortic dissection.

PubMed

Huawei, P; Qian, C; Chuan, T; Lei, L; Laing, W; Wenlong, X; Wenzhi, L

2014-02-01

In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

Preservation of the bicuspid aortic valve.

PubMed

Schäfers, Hans-Joachim; Aicher, Diana; Langer, Frank; Lausberg, Henning F

2007-02-01

Bicuspid anatomy of the aortic valve is a common reason for aortic regurgitation and is associated with aortic dilatation in more than 50% of patients. We have observed different patterns of aortic dilatation and used different approaches preserving the valve. Between October 1995 and February 2006, a regurgitant bicuspid valve was repaired in 173 patients. The aorta was normal in 57 patients who underwent isolated repair. Aortic dilatation mainly above commissural level (n = 38) was treated by separate valve repair plus supracommissural aortic replacement. In 78 patients, aortic dilatation involved the root and was treated by root remodeling. Hospital mortality and perioperative morbidity were low in all three groups. Myocardial ischemia was significantly shorter in repair plus aortic replacement than remodeling (p < 0.001). Freedom from aortic regurgitation II or greater at 5 years varied between 91% and 96%. Freedom from reoperation at 5 years was 97% after remodeling, but only 53% after repair plus aortic replacement (p = 0.33). Symmetric prolapse was the most frequent cause for reoperation. The long-term stability of bicuspid aortic valve repair is excellent in the absence of aortic pathology. In the presence of aortic dilatation, root remodeling leads to equally stable valve durability. In patients with less pronounced root dilatation, separate valve repair plus aortic replacement may be a less complex alternative. Symmetric prolapse should be avoided if the ascending aorta is replaced.

Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

ClinicalTrials.gov

2017-04-26

Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

A novel approach: trans-ascending aorta balloon aortic valvuloplasty via sternotomy for treating severe valvular aortic stenosis in a low-weight infant.

PubMed

Gao, Lei; Wu, Qin; Xu, Xinhua; Zhao, Tianli; Jin, Wancun; Yang, Yifeng

2014-02-01

Severe congenital aortic stenosis in infants is a life-threatening congenital heart anomaly that is typically treated using percutaneous balloon aortic valvuloplasty. The usual route is the femoral artery under radiographic guidance. However, this procedure may be limited by the small size of the femoral artery in low-weight infants. An infant weighing only 7 kg with severe aortic stenosis (peak gradient was 103 mmHg) was successfully treated with a novel approach, that is trans-ascending aorta balloon aortic valvuloplasty guided by transesophageal echocardiography. The patient tolerated the procedure well, and no major complications developed. After the intervention, transesophageal echocardiography indicated a significant reduction of the aortic valvular peak gradient from 103 mmHg to 22 mmHg, no aortic regurgitation was found. Eighteen months after the intervention, echocardiography revealed that the aortic valvular peak gradient had increased to 38 mmHg and that still no aortic regurgitation had occurred. In our limited experience, trans-ascending aorta balloon aortic valvuloplasty for severe aortic stenosis under transesophageal echocardiography guidance effectively reduces the aortic peak gradient. As this is a new procedure, long-term follow up and management will need to be established. It may be an alternative technique to treat congenital aortic stenosis in low-weight patients.

Pharmacological endothelin receptor interaction does not occur in veins from ET(B) receptor deficient rats.

PubMed

Thakali, Keshari; Galligan, James J; Fink, Gregory D; Gariepy, Cheryl E; Watts, Stephanie W

2008-07-01

Heterodimerization of G-protein coupled receptors can alter receptor pharmacology. ET A and ET B receptors heterodimerize when co-expressed in heterologous expression lines. We hypothesized that ET A and ET B receptors heterodimerize and pharmacologically interact in vena cava from wild-type (WT) but not ET B receptor deficient (sl/sl) rats. Pharmacological endothelin receptor interaction was assessed by comparing ET-1-induced contraction in rings of rat thoracic aorta and thoracic vena cava from male Sprague Dawley rats under control conditions, ET A receptor blockade (atrasentan, 10 nM), ET B receptor blockade (BQ-788, 100 nM) or ET B receptor desensitization (Sarafotoxin 6c, 100 nM) and ET A plus ET B receptor blockade or ET A receptor blockade plus ET B receptor desensitization. In addition, similar pharmacological ET receptor antagonism experiments were performed in rat thoracic aorta and vena cava from WT and sl/sl rats. ET A but not ET B receptor blockade or ET B receptor desensitization inhibited aortic and venous ET-1-induced contraction. In vena cava but not aorta, when ET B receptors were blocked (BQ-788, 100 nM) or desensitized (S6c, 100 nM), atrasentan caused a greater inhibition of ET-1-induced contraction. Vena cava from WT but not sl/sl rats exhibited similar pharmacological ET receptor interaction. Immunocytochemistry was performed on freshly dissociated aortic and venous vascular smooth muscle cells to determine localization of ET A and ET B receptors. ET A and ET B receptors qualitatively co-localized more strongly to the plasma membrane of aortic compared to venous vascular smooth muscle cells. Our data suggest that pharmacological ET A and ET B receptor interaction may be dependent on the presence of functional ET B receptors and independent of receptor location.

Double aortic arch

MedlinePlus

Aortic arch anomaly; Double arch; Congenital heart defect - double aortic arch; Birth defect heart - double aortic arch ... aorta is a single arch that leaves the heart and moves leftward. In double aortic arch, some ...

Outcomes After Operations for Unicuspid Aortic Valve With or Without Ascending Repair in Adults

PubMed Central

Zhu, Yuanjia; Roselli, Eric E.; Idrees, Jay J.; Wojnarski, Charles M.; Griffin, Brian; Kalahasti, Vidyasagar; Pettersson, Gosta; Svensson, Lars G.

2016-01-01

Background Unicuspid aortic valve is an important subset of bicuspid aortic valve, and knowledge regarding its aortopathy pattern and surgical outcomes is limited. Our objectives were to characterize unicuspid aortic valve patients, associated aortopathy, and surgical outcomes. Methods From January 1990 to May 2013, 149 adult unicuspid aortic valve patients underwent aortic valve replacement or repair for aortic stenosis (n = 13), regurgitation (n = 13), or both (n = 123), and in 91 (61%) the aortic valve operation was combined with aortic repair. Data were obtained from the Cardiovascular Information Registry and medical record review. Three-dimensional imaging analysis was performed from preoperative computed tomography and magnetic resonance imaging scans. The Kaplan-Meier method was used for survival analysis. Results Patients had a mean maximum aortic diameter of 44 ± 8 mm and variably involved the aortic root, ascending, or arch, or both. Patients with valve operations alone were more likely to be hypertensive (p = 0.01) and to have severe aortic stenosis (p = 0.07) than those who underwent concurrent aortic operations. There were no operative deaths, strokes, or myocardial infarctions. Patients undergoing aortic repair had better long-term survival. Estimated survival at 1, 5, and 10 years was 100%, 100%, and 100% after combined operations and was 100%, 88%, and 88% after valve operations alone (p = 0.01). Conclusions Patients with a dysfunctional unicuspid aortic valve frequently present with an ascending aneurysm that requires repair. Combined aortic valve operations and aortic repair was associated with significantly better long-term survival than a valve operation alone. Further study of this association may direct decisions about timing of surgical intervention. PMID:26453423

Degree of fusiform dilatation of the proximal descending aorta in type B acute aortic dissection can predict late aortic events.

PubMed

Marui, Akira; Mochizuki, Takaaki; Koyama, Tadaaki; Mitsui, Norimasa

2007-11-01

Predicting the risk factors for late aortic events in patients with type B acute aortic dissection without complications may help to determine a therapeutic strategy for this disorder. We investigated whether late aortic events in type B acute aortic dissection can be predicted accurately by an index that expresses the degree of fusiform dilatation of the proximal descending aorta during the acute phase; this index can be calculated as follows: (maximum diameter of the proximal descending aorta)/(diameter of the distal aortic arch + diameter of the descending aorta at the pulmonary artery level). Patients with type B acute aortic dissection without complications (n = 141) were retrospectively analyzed to determine the predictors of late aortic events; these include aortic dilatation, rupture, refractory pain, organ ischemia, rapid aortic enlargement, and rapid enlargement of ulcer-like projections. The fusiform index in patients with late aortic events (0.59) was higher than that in patients without late aortic events (0.53, P < .01). Patients with a higher fusiform index exhibited aortic dilatation earlier than those with a lower fusiform index. By multivariate analysis, we conclude that the predominant independent predictors of late aortic events were a maximum aortic diameter of 40 mm or more, a patent false lumen, and a fusiform index of 0.64 or more (hazard ratios, 3.18, 2.64, and 2.73, respectively). The values of actuarial freedom from aortic events for patients with all 3 predictors at 1, 5, and 10 years were 22%, 17%, and 8%, respectively, whereas the values in those without these predictors were 97%, 94%, and 90%, respectively. The degree of fusiform dilatation of the proximal descending aorta, a patent false lumen, and a large aortic diameter can be predominant predictors of late aortic events in patients with type B acute aortic dissection. Patients with these predictors should be recommended to undergo early interventions (surgery or stent-graft implantation) or at least be closely followed up during the chronic phase before such events develop.

Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B Aortic Dissection with Severe Limb Ischemia.

PubMed

Higuchi, Yoshiro; Tochii, Masato; Takami, Yoshiyuki; Kobayashi, Akihiro; Yanagisawa, Tsutomu; Amano, Kentaro; Sakurai, Yusuke; Ishida, Michiko; Ishikawa, Hiroshi; Hattori, Koji; Takagi, Yasushi

2017-03-24

We report a rare case of retrograde Stanford type A aortic dissection after endovascular repair for complicated Stanford type B aortic dissection. A 45-year-old man presented with a sudden onset of back pain and was transferred to our hospital. Computed tomography demonstrated acute Stanford type B aortic dissection with lower limb ischemia. Emergency endovascular surgery was planned for repair of the Stanford type B aortic dissection. The patient suddenly developed recurrent chest pain 10 days after the initial procedure. Computed tomography revealed retrograde Stanford type A aortic dissection involving the ascending aorta and aortic arch. The patient underwent a successful emergency total aortic arch replacement.

Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension

PubMed Central

Costa, Tiago J.; Ceravolo, Graziela S.; Echem, Cinthya; Hashimoto, Carolina M.; Costa, Beatriz P.; Santos-Eichler, Rosangela A.; Oliveira, Maria Aparecida; Jiménez-Altayó, Francesc; Akamine, Eliana H.; Dantas, Ana Paula; Carvalho, Maria Helena C.

2018-01-01

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P-450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P-450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 μg/Kg/day/po] or CEE associated to testosterone [(CEE+T) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEE+T abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 μM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEE+T group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEE+T. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone. PMID:29867542

Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension.

PubMed

Costa, Tiago J; Ceravolo, Graziela S; Echem, Cinthya; Hashimoto, Carolina M; Costa, Beatriz P; Santos-Eichler, Rosangela A; Oliveira, Maria Aparecida; Jiménez-Altayó, Francesc; Akamine, Eliana H; Dantas, Ana Paula; Carvalho, Maria Helena C

2018-01-01

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P -450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P -450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 μg/Kg/day/po] or CEE associated to testosterone [(CEE+T) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEE+T abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 μM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEE+T group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEE+T. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone.

DW10075, a novel selective and small-molecule inhibitor of VEGFR, exhibits antitumor activities both in vitro and in vivo

PubMed Central

Li, Meng-yuan; Lv, Yong-cong; Tong, Lin-jiang; Peng, Ting; Qu, Rong; Zhang, Tao; Sun, Yi-ming; Chen, Yi; Wei, Li-xin; Geng, Mei-yu; Duan, Wen-hu; Xie, Hua; Ding, Jian

2016-01-01

Aim: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. Methods: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg·kg−1·d−1, po) for two weeks. Results: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 μmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1–100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 μmol/L (for U87-MG human glioblastoma cells) to 22.2 μmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. Conclusion: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development. PMID:26806300

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats.

PubMed

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats

PubMed Central

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance. PMID:28453571

Geraniol improves the impaired vascular reactivity in diabetes and metabolic syndrome through calcium channel blocking effect.

PubMed

El-Bassossy, Hany M; Elberry, Ahmed A; Ghareib, Salah A

2016-08-01

The aim of the present study is to investigate the effect and possible mechanism of action of geraniol on the impaired vascular reactivity of aortic rings isolated from diabetes or metabolic syndrome (MS) -induced rats. Male Wistar rats were divided into control, type 1 diabetes and metabolic syndrome (MS) groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50mg/kg) and left for 10weeks to develop vascular complications. MS was induced by adding 10% fructose and 3% salt to water and diet for 12weeks. The present study investigated the effect of in vitro incubation with geraniol (10-300μM) on the vasoconstrictor response to phenylephrine (PE) and the vasodilator response to acetylcholine (ACh) as well as its effect on aortae incubated with methylglyoxal (MG) as an advanced glycation end product (AGE). To investigate the mechanism of action of geraniol, different blockers are used, including Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100μM), tetraethylammonium chloride (TEA, 10mM), and indomethacin (INDO, 5μM). Moreover, the effect of calcium chloride (CaCl2) on aortic rings precontracted with PE or potassium chloride (KCl) was examined. Thirty minutes incubation with geraniol alleviated the exaggerated vasoconstriction in aortae isolated from diabetic or MS animals or in vitro exposed to MG in a concentration-dependent manner. In addition, geraniol improved the vasodilatation response of diabetic or MS aortae or aortae exposed to MG. In search for the mechanism; geraniol produced concentration-dependent relaxation of both PE and KCl-precontracted aorta. Geraniol relaxation was not affected by L-NAME, INDO or TEA. However, geraniol significantly inhibited voltage dependent and receptor mediated Ca(2+)-induced contraction activated by KCl or PE respectively. In conclusion, geraniol ameliorates impaired vascular reactivity in experimentally induced diabetes and MS. The effect may be partially attributed to an endothelium-independent pathway involving blockage of both voltage dependent and receptor operated calcium channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism.

PubMed

Ch'ng, Yung Sing; Loh, Yean Chun; Tan, Chu Shan; Ahmad, Mariam; Asmawi, Mohd Zaini; Wan Omar, Wan Maznah; Yam, Mun Fei

2017-12-01

Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia. This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint. Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists. The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC 50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC 50 0.971 ± 0.459 mg/mL), methylene blue (EC 50 1.203 ± 0.426 mg/mL), indomethacin (EC 50 2.128 ± 1.218 mg/mL), atropine (EC 50 0.470 ± 0.325 mg/mL), and propranolol (EC 50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC 50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca 2+ released from the sarcoplasmic reticulum and blocking calcium channels. The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI 2 signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β 2 -adrenergic receptor levels.

Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm.

PubMed

Roberts, William Clifford; Vowels, Travis James; Ko, Jong Mi; Filardo, Giovanni; Hebeler, Robert Frederick; Henry, Albert Carl; Matter, Gregory John; Hamman, Baron Lloyd

2011-03-01

There is debate concerning whether an aneurysmal ascending aorta should be replaced when associated with a dysfunctioning aortic valve that is to be replaced. To examine this issue, we divided the patients by type of aortic valve dysfunction-either aortic stenosis (AS) or pure aortic regurgitation (AR)-something not previously undertaken. Of 122 patients with ascending aortic aneurysm (unassociated with aortitis or acute dissection), the aortic valve was congenitally malformed (unicuspid or bicuspid) in 58 (98%) of the 59 AS patients, and in 38 (60%) of the 63 pure AR patients. Ascending aortic medial elastic fiber loss (EFL) (graded 0 to 4+) was zero or 1+ in 53 (90%) of the AS patients, in 20 (53%) of the 38 AR patients with bicuspid valves, and in all 12 AR patients with tricuspid valves unassociated with the Marfan syndrome. An unadjusted analysis showed that, among the 96 patients with congenitally malformed valves, the 38 AR patients had a significantly higher likelihood of 2+ to 4+ EFL than the 58 AS patients (crude odds ratio: 8.78; 95% confidence interval: 2.95, 28.13). These data strongly suggest that the type of aortic valve dysfunction-AS versus pure AR-is very helpful in predicting loss of aortic medial elastic fibers in patients with ascending aortic aneurysms and aortic valve disease.

Vasorelaxant effects of grape polyphenols in rat isolated aorta. Possible involvement of a purinergic pathway.

PubMed

Mendes, Anne; Desgranges, Claude; Chèze, Catherine; Vercauteren, Joseph; Freslon, Jean-Louis

2003-12-01

The purpose of this study was to investigate the mechanism of the vascular relaxation produced by polyphenolic substances from red wine, with a particular focus on the possible involvement of purinoceptors. With this aim, relaxing responses induced by procyanidin from grape seeds (GSP), anthocyanins, catechin and epicatechin were assessed in rat isolated aortic rings left intact (+E) or endothelium-denuded (-E). In preparations precontracted with noradrenaline, incubation with NG-nitro-L-arginine methyl ester (100 microM, 30 min) fully inhibited the GSP-induced relaxations. Concentration-effect curves to these substances (from 10(-7) to 10(-1) g/L) were determined in depolarized (60 mM KCl) preparations in control condition, after incubation with reactive blue 2 (an antagonist of P2Y purinoceptors, 30 microM), with apyrase (an enzyme which hydrolyses ATP and ADP, 0.8 U/mL) or with alpha,beta-methylene ATP (an inhibitor of ecto ATPases, 10 microM). In (+E) rings, relaxations (expressed as percentage of initial contraction) were 41 +/- 2 and 37 +/- 3 for GSP and anthocyanins, respectively. Only modest relaxations (ca. 10%) were observed in (-E) rings, as it was the case for catechin and epicatechin in (+/- E) rings. Reactive blue 2 or apyrase inhibited the GSP- and anthocyanin-induced relaxations in (+E) rings, while alpha,beta-methylene ATP shifted to the left the relaxation curves obtained with GSP. These data confirm that modest relaxations observed with catechin and epicatechin are not endothelium-dependent but that GSP and anthocyanins induce a relaxing effect, which is related to the integrity of the endothelium and the synthesis and release of nitric oxide (NO). Furthermore, the inhibition by apyrase and the increase by ecto-ATPase inhibition of the GSP- and anthocyanin-induced relaxation suggest that these substances could act via an initial release of nucleotides, which in turn could activate P2Y1 and/or P2Y2 purinoceptors of endothelial cells, trigger the synthesis and release of NO and then lead to relaxation.

Effectiveness of open versus endovascular abdominal aortic aneurysm repair in population settings: A systematic review of statewide databases.

PubMed

Williams, Christopher R; Brooke, Benjamin S

2017-10-01

Patient outcomes after open abdominal aortic aneurysm and endovascular aortic aneurysm repair have been widely reported from several large, randomized, controlled trials. It is not clear whether these trial outcomes are representative of abdominal aortic aneurysm repair procedures performed in real-world hospital settings across the United States. This study was designed to evaluate population-based outcomes after endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair using statewide inpatient databases and examine how they have helped improve our understanding of abdominal aortic aneurysm repair. A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify articles comparing endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using data from statewide inpatient databases. This search was limited to studies published in the English language after 1990, and abstracts were screened and abstracted by 2 authors. Our search yielded 17 studies published between 2004 and 2016 that used data from 29 different statewide inpatient databases to compare endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. These studies support the randomized, controlled trial results, including a lower mortality associated with endovascular aortic aneurysm repair extended from the perioperative period up to 3 years after operation, as well as a higher complication rate after endovascular aortic aneurysm repair. The evidence from statewide inpatient database analyses has also elucidated trends in procedure volume, patient case mix, volume-outcome relationships, and health care disparities associated with endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. Population analyses of endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using statewide inpatient databases have confirmed short- and long-term mortality outcomes obtained from large, randomized, controlled trials. Moreover, these analyses have allowed us to assess the effect of endovascular aortic aneurysm repair adoption on population outcomes and patient case mix over time. Published by Elsevier Inc.

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report.

PubMed

Kamran, Mudassar; Fowler, Kathryn J; Mellnick, Vincent M; Sicard, Gregorio A; Narra, Vamsi R

2016-06-01

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model.

PubMed

Poullis, Michael P; Warwick, Richard; Oo, Aung; Poole, Robert J

2008-06-01

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

Aortic assessment of bicuspid aortic valve patients and their first-degree relatives.

PubMed

Straneo, Pablo; Parma, Gabriel; Lluberas, Natalia; Marichal, Alvaro; Soca, Gerardo; Cura, Leandro; Paganini, Juan J; Brusich, Daniel; Florio, Lucia; Dayan, Victor

2017-03-01

Background Bicuspid aortic valve patients have an increased risk of aortic dilatation. A deficit of nitric oxide synthase has been proposed as the causative factor. No correlation between flow-mediated dilation and aortic diameter has been performed in patients with bicuspid aortic valves and normal aortic diameters. Being a hereditary disease, we compared echocardiographic features and endothelial function in these patients and their first-degree relatives. Methods Comprehensive physical examinations, routine laboratory tests, transthoracic echocardiography, and measurements of endothelium-dependent and non-dependent flow-mediated vasodilatation were performed in 18 bicuspid aortic valve patients (14 type 1 and 4 type 2) and 19 of their first-degree relatives. Results The first-degree relatives were younger (36.7 ± 18.8 vs. 50.5 ± 13.9 years, p = 0.019) with higher ejection fractions (64.6% ± 1.7% vs. 58.4% ± 9.5%, p = 0.015). Aortic diameters indexed to body surface area were similar in both groups, the except the tubular aorta which was larger in bicuspid aortic valve patients (19.3 ± 2.7 vs. 17.4 ± 2.2 mm·m -2 , p = 0.033). Flow-dependent vasodilation was similar in both groups. A significant inverse correlation was found between non-flow-dependent vasodilation and aortic root diameter in patients with bicuspid aortic valve ( R = -0.57, p = 0.05). Conclusions Bicuspid aortic valve patients without aortopathy have larger ascending aortic diameters than their first-degree relatives. Endothelial function is similar in both groups, and there is no correlation with ascending aorta diameter. Nonetheless, an inverse correlation exists between non-endothelial-dependent dilation and aortic root diameter in bicuspid aortic valve patients.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With Bicuspid Aortic Valve and a Dilated Ascending Aorta.

PubMed

Masri, Ahmad; Kalahasti, Vidyasagar; Svensson, Lars G; Alashi, Alaa; Schoenhagen, Paul; Roselli, Eric E; Johnston, Douglas R; Rodriguez, L Leonardo; Griffin, Brian P; Desai, Milind Y

2017-06-01

In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height. We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm 2 /m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6-12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20-3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26-0.80) was associated with improved survival (both P <0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio. In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death. © 2017 American Heart Association, Inc.

Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults.

PubMed

Hughes, William E; Ueda, Kenichi; Treichler, David P; Casey, Darren P

2016-09-30

Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Alcohol consumption and mortality from aortic disease among Japanese men: The Japan Collaborative Cohort study.

PubMed

Shirakawa, Toru; Yamagishi, Kazumasa; Yatsuya, Hiroshi; Tanabe, Naohito; Tamakoshi, Akiko; Iso, Hiroyasu

2017-11-01

Only a few population-based prospective studies have examined the association between alcohol consumption and abdominal aortic aneurysm, and the results are inconsistent. Moreover, no evidence exists for aortic dissection. We examined the effect of alcohol consumption on risk of mortality from aortic diseases. A total of 34,720 men from the Japan Collaborative Cohort study, aged 40-79 years, without history of cardiovascular disease and cancer at baseline 1988 and 1990 were followed up until the end of 2009 for their mortality and its underlying cause. Hazard ratios of mortality from aortic diseases were estimated according to alcohol consumption categories of never-drinkers, ex-drinkers, regular drinkers of ≤30 g, and >30 g ethanol per day. During the median 17.9-year follow-up period, 45 men died of aortic dissection and 41 men died of abdominal aortic aneurysm. Light to moderate drinkers of ≤30 g ethanol per day had lower risk of mortality from total aortic disease and aortic dissection compared to never-drinkers. The respective multivariable hazard ratios (95% confidence intervals) were 0.46 (0.28-0.76) for total aortic disease and 0.16 (0.05-0.50) for aortic dissection. Heavy drinkers of >30 g ethanol per day did not have reduced risk of mortality from total aortic disease, albeit had risk variation between aortic dissection and abdominal aortic aneurysm. Light to moderate alcohol consumption was associated with reduced mortality from aortic disease among Japanese men. Copyright © 2017. Published by Elsevier B.V.

L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

PubMed

Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

2018-03-01

The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine by L-arginine depends on arginase activity and the production of urea and ornithine.

Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate.

PubMed

de Fátima Reis, Carolina; de Andrade, Daniela Medeiros Lobo; Junior Neves, Bruno; de Almeida Ribeiro Oliveira, Leandra; Pinho, José Felippe; da Silva, Leidiane Pinha; Dos Santos Cruz, Jader; Bara, Maria Teresa Freitas; Andrade, Carolina Horta; Rocha, Matheus Lavorenti

2015-10-01

Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 μg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 μg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 μM), phenylephrine (0.1 μM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2). Copyright © 2015 Elsevier Ltd. All rights reserved.

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

PubMed Central

Schipke, J. D.; Korbmacher, B.; Dorszewski, A.; Selcan, G.; Sunderdiek, U.; Arnold, G.

1996-01-01

OBJECTIVE--To amplify the description of myocardial stunning. DESIGN--Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS--15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES--Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS--Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS--Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus. Images PMID:8624873

Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus formation.

PubMed

Giroux, Sylvie K; Labinaz, Marino X; Grisoli, Dominique; Klug, Andrew P; Veinot, John P; Burwash, Ian G

2010-01-01

Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. Pannus formation usually restricts systolic excursion of the occluding disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus formation. We describe an unusual case of intermittent, noncyclic dysfunction of a mechanical aortic prosthesis due to pannus formation in the absence of systolic restriction of disk excursion that presented with intermittent massive aortic regurgitation, severe ischemia, and shock. Pannus formation should be considered as a potential cause of acute intermittent severe aortic regurgitation in a patient with a mechanical aortic prosthesis.

Snare-assisted anterograde balloon mitral and aortic valvotomy using Inoue balloon catheter.

PubMed

Krishnan, Mangalath N; Syamkumar, M D; Sajeev, C G; Venugopal, K; Johnson, Francis; Vinaykumar, D; Velayudhan, C C; Jayakumar, T G

2007-01-02

We performed concurrent antegrade mitral and aortic valvotomy using Inoue dilatation catheter in 3 cases of combined rheumatic mitral and aortic stenosis. Following mitral valvotomy by standard procedure, aortic valve was crossed with the help of a floatation catheter. Stiff long length guide wire was fixed in descending aorta using a snare. Inoue catheter was threaded over the wire across the aortic valve and aortic valvotomy completed. Mitral valve area increased from mean 1 cm2 to 2 cm2; aortic gradient dropped from mean of 97 mm to 36 mm. Concurrent anterograde balloon mitral and aortic valvotomy may be effective and safe.

Variant Rabbit Hemorrhagic Disease Virus in Young Rabbits, Spain

PubMed Central

Dalton, Kevin P.; Nicieza, Inés; Balseiro, Ana; Muguerza, María A.; Rosell, Joan M.; Casais, Rosa; Álvarez, Ángel L.

2012-01-01

Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen. PMID:23171812

Vasodilator activity of the essential oil from aerial parts of Pectis brevipedunculata and its main constituent citral in rat aorta.

PubMed

Pereira, Sharlene Lopes; Marques, André Mesquita; Sudo, Roberto Takashi; Kaplan, Maria Auxiliadora Coelho; Zapata-Sudo, Gisele

2013-03-07

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p < 0.05), respectively. The IC50 values for citral in endothelium-intact and denuded rings were 0.024% ± 0.004% and 0.021% ± 0.004%, respectively (p > 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Effect of Cymbopogon citratus and Citral on Vascular Smooth Muscle of the Isolated Thoracic Rat Aorta.

PubMed

Devi, R Chitra; Sim, S M; Ismail, R

2012-01-01

Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose-dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium-independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE.