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Sample records for rat basilar artery

  1. The role of Na(+), K(+)-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery.

    PubMed

    Shen, Haitao; Liang, Peng; Qiu, Suhua; Zhang, Bo; Wang, Yongli; Lv, Ping

    2016-06-01

    Hypoxia-induced cerebrovascular dysfunction is a key factor in the occurrence and the development of cerebral ischemia. Na(+), K(+)-ATPase affects the regulation of intracellular Ca(2+) concentration and plays an important role in vascular smooth muscle function. However, the potential role of Na(+), K(+)-ATPase in hypoxia-induced cerebrovascular dysfunction is unknown. In this study, we found that the KCl-induced contraction under hypoxia in rat endothelium-intact basilar arteries is similar to that of denuded arteries, suggesting that hypoxia may cause smooth muscle cell (SMC)-dependent vasoconstriction in the basilar artery. The Na(+), K(+)-ATPase activity of the isolated basilar artery with or without endothelium significantly reduced with prolonged hypoxia. Blocking the Na(+)-Ca(2+) exchanger with Ni(2+) (10(-3)M) or the L-type Ca(2+) channel with nimodipine (10(-8)M) dramatically attenuated KCl-induced contraction under hypoxia. Furthermore, prolonged hypoxia significantly reduced Na(+), K(+)-ATPase activity and increased [Ca(2+)]i in cultured rat basilar artery SMCs. Hypoxia reduced the protein and mRNA expression of the α2 isoform of Na(+), K(+)-ATPase in SMCs in vitro. We used a low concentration of the Na(+), K(+)-ATPase inhibitor ouabain, which possesses a high affinity for the α2 isoform. The contractile response in the rat basilar artery under hypoxia was partly inhibited by ouabain pretreatment. The decreased Na(+), K(+)-ATPase activity in isolated basilar artery and the increased [Ca(2+)]i in SMCs induced by hypoxia were partly inhibited by pretreatment with a low concentration of ouabain. These results suggest that hypoxia may educe Na(+), K(+)-ATPase activity in SMCs through the α2 isoform contributing to vasoconstriction in the rat basilar artery.

  2. [Effects of calcium-activated chloride channels on vascular activity of rat cerebral basilar artery].

    PubMed

    Wang, Rui; Li, Li; Ma, Ke-Tao; Si, Jun-Qiang

    2014-06-25

    This study investigated the role of calcium-activated Cl⁻ channels (CaCCs) in mediating vasomotor activity of cerebral basilar artery (BA) of Wistar rat. Pressure myograph was used to examine the changes in diameter of isolated BA to vasoactive reagents. The results showed that (1) The rate of pressure-induced vasomotor activity was 78.6% (n = 28) in BA from 0 to 100 mmHg working pressure. The contractile phase of the response was faster than the relaxation phase; (2) The amplitude of contraction was (62.6 ± 6.4) µm (n = 22), the frequency of contraction was variable and the highest value was 8.0 ± 2.3 per 5 min at 60 mmHg working pressure (n = 22); (3) The pressure-induced vasomotor activity of BA was markedly attenuated when Ca²⁺ was removed from medium; (4) The pressure-induced vasomotor activity was blocked by voltage dependent Ca²⁺ channel blocker nimodipine; (5) The pressure-induced vasomotor was inhibited by CaCC antagonists NFA and NPPB. These results suggest that the pressure-induced vasomotor activity of isolated BA is associated with Ca²⁺ influx that activates CaCCs.

  3. Hyperdensity of the Basilar Artery on Postmortem CT: A Potential Indicator for Basilar Artery Thrombosis.

    PubMed

    Garland, Jack; Tse, Rexson; Beh, Raymond J; Lyons, Timothy J; Cala, Allan D

    2016-06-01

    Basilar artery thrombosis constitutes 1% of all types of stroke, carries a mortality rate of up to 90%, and is one of the rarer causes of sudden death. It leads to brain stem ischemia and commonly presents with impaired consciousness, cranial nerve palsy, hemiplegia or quadriplegia, and sudden collapse. Clinically, the diagnosis of basilar artery thrombosis is made on clinical symptoms, along with a hyperdense basilar artery in antemortem computed tomography (CT) scan. To our knowledge, whether a hyperdense basilar artery indicates basilar artery thrombosis on postmortem CT scan is not documented in the literature. We present a case report of a 55-year-old man who on postmortem CT scan showed a hyperdense basilar artery and was subsequently confirmed to be a fatal basilar artery thrombosis. We suggest that a hyperdense basilar artery on postmortem CT should prompt the pathologist to consider basilar artery thrombosis. PMID:27049662

  4. Alterations in the expression of protease-activated receptor 1 and tumor necrosis factor-α in the basilar artery of rats following a subarachnoid hemorrhage

    PubMed Central

    LI, GANG; WANG, QING-SONG; LIN, TING-TING

    2016-01-01

    The present study aimed to investigate the expression of protease-activated receptor 1 (PAR1) and tumor necrosis factor (TNF)-α in a rat model of subarachnoid hemorrhage (SAH)-induced cerebral vasospasm (CVS). The rat models were established by twice injecting blood into the cisterna magna, after which the following experimental groups were established: The normal group, the SAH3d group, the SAH5d group and the SAH7d group. The rats were perfused and the basilar artery was removed for histological examination. The cross-sectional area of the basilar artery lumen was measured using computer software; and the protein expression of PAR1 and TNF-α was detected by immunohistochemistry. The cross-sectional area of the basilar artery of the rats in the SAH model groups was significantly decreased in a time-dependent manner, as compared with the normal group. The protein expression of PAR1 and TNF-α in the SAH3d, SAH5d and SAH7d groups was significantly increased over time (P<0.05), as compared with the normal group. CVS was detected in the basilar artery, and was associated with wall thickening and significant narrowing of the lumen, thus suggesting that the present model may be used for investigating cerebrovascular disease following SAH. The immunohistochemical analyses demonstrated that the protein expression of PAR1 and TNF-α was significantly increased in the basilar artery of the SAH model rats, and were positively correlated with the degree of CVS. PMID:26997984

  5. Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions.

    PubMed

    Allen, Tracy; Iftinca, Mircea; Cole, William C; Plane, Frances

    2002-12-15

    The release of endothelium-derived relaxing factors, such as nitric oxide (NO), is dependent on an increase in intracellular calcium levels ([Ca(2+)](i)) within endothelial cells. Endothelial cell membrane potential plays a critical role in the regulation of [Ca(2+)](i) in that calcium influx from the extracellular space is dependent on membrane hyperpolarization. In this study, the effect of inhibition of vascular smooth muscle delayed rectifier K(+) (K(DR)) channels by 4-aminopyridine (4-AP) on endothelium-dependent relaxation of rat basilar artery to acetylcholine (ACh) was assessed. ACh-evoked endothelium-dependent relaxations were inhibited by N-(Omega)-nitro-L-arginine (L-NNA) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), confirming a role for NO and guanylyl cyclase. 4-AP (300 microM) also suppressed ACh-induced relaxation, with the maximal response reduced from approximately 92 to approximately 33 % (n = 11; P < 0.01). However, relaxations in response to exogenous NO, applied in the form of authentic NO, sodium nitroprusside or diethylamineNONOate (DEANONOate), were not affected by 4-AP treatment (n = 3-11). These data are not consistent with the view that 4-AP-sensitive K(DR) channels are mediators of vascular hyperpolarization and relaxation in response to endothelium-derived NO. Inhibition of ACh-evoked relaxation by 4-AP was reversed by pinacidil (0.5-1 microM; n = 5) or 18beta-glycyrrhetinic acid (18betaGA; 5 microM; n = 5), indicating that depolarization and electrical coupling of the smooth muscle to the endothelium were involved. 4-AP caused depolarization of both endothelial and vascular smooth muscle cells of isolated segments of basilar artery (mean change 11 +/- 1 and 9 +/- 2 mV, respectively; n = 15). Significantly, 18betaGA almost completely prevented the depolarization of endothelial cells (n = 6), but not smooth muscle cells (n = 6) by 4-AP. ACh-induced hyperpolarization of endothelium and smooth muscle cells was also reduced by 4-AP

  6. Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.

    PubMed

    Yoon, SeongHun; Gariepy, Cheryl E; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M

    2016-03-01

    The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

  7. From basilar artery dolichoectasia to basilar artery aneurysm: natural history in images.

    PubMed

    Zis, Panagiotis; Fragkis, Stylianos; Lykouri, Maria; Bageris, Ioannis; Kolovos, Georgios; Angelidakis, Panagiotis; Tavernarakis, Antonios

    2015-05-01

    Dolichoectasia is a medical term used to describe elongated and dilated vessels that follow a tortuous and windy course with frequent loops and curves. We are presenting the natural history in images of a normal basilar artery becoming dolichoectatic, followed by the formation of an aneurysm, over a period of many years, in 60-year-old Caucasian man with a long history of secondary progressive multiple sclerosis and uncontrolled arterial hypertension, who was diagnosed with dolichoectasia of basilar artery in 2008. Although relatively stable at this point, eventually his mobility deteriorated and signs from the cranial nerves, such as trigeminal neuralgia and bilateral palsy of the VI and the VII nerves were added in the clinical picture. In 2014, both computed tomography and magnetic resonance imaging of the brain revealed the formation of an unruptured aneurysm of the basilar artery.

  8. Basilar artery of the capybara (Hydrochaeris hydrochaeris): an ultrastructural study.

    PubMed

    Islam, S; Ribeiro, A A C M; Loesch, A

    2004-04-01

    The present study investigated the ultrastructural features of the basilar artery of the largest rodent species, the capybara. The study suggests that the general ultrastructural morphological organization of the basilar artery of the capybara is similar to that of small rodents. However, there are some exceptions. The basilar artery of the capybara contains a subpopulation of 'granular' vascular smooth muscle cells resembling monocytes and/or macrophages. The possibility cannot be excluded that the presence of these cells reflects the remodelling processes of the artery due to animal maturation and the regression of the internal carotid artery. To clarify this issue, more systemic studies are required involving capybaras of various ages.

  9. Basilar artery thrombosis in the setting of antiphospholipid syndrome.

    PubMed

    Saad, Amin F; Nickell, Larry T; Heithaus, R Evans; Shamim, Sadat A; Opatowsky, Michael J; Layton, Kennith F

    2014-07-01

    Antiphospholipid syndrome is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent first-trimester pregnancy loss, and multiple additional clinical manifestations. We describe a man with severe atherosclerotic basilar artery stenosis and superimposed in situ thrombus who was found to have antiphospholipid syndrome.

  10. Basilar artery thrombosis in the setting of antiphospholipid syndrome

    PubMed Central

    Nickell, Larry T.; Heithaus, R. Evans; Shamim, Sadat A.; Opatowsky, Michael J.; Layton, Kennith F.

    2014-01-01

    Antiphospholipid syndrome is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent first-trimester pregnancy loss, and multiple additional clinical manifestations. We describe a man with severe atherosclerotic basilar artery stenosis and superimposed in situ thrombus who was found to have antiphospholipid syndrome. PMID:24982561

  11. Growth of basilar artery aneurysm after ventriculo-peritoneal shunt.

    PubMed

    Kim, Myoung Soo; Oh, Chang-Wan; Han, Dae Hee

    2002-11-01

    We report upon two cases of obstructive hydrocephalus produced by giant basilar artery aneurysms. They initially presented with symptoms of increased intracranial pressure, and were managed by a ventriculo-peritoneal (VP) shunt with good symptomatic improvement. With time, however, both showed a gradual deterioration of clinical symptoms due to increased aneurysm size. One, with a basilar tip aneurysm was treated by direct neck-clipping of the aneurysm, and was able to return to work. In the other patient, with a basilar trunk aneurysm, endovascular occlusion of one vertebral artery was attempted in an effort to decrease the aneurysm size, but the aneurysm enlarged precipitating brain stem failure. In conclusion, these cases reveal the risk of the VP shunt, which may induce aneurysmal growth, leading to clinical devastation, and emphasize the importance of definitive treatment for giant cerebral aneurysms whenever possible.

  12. Intravascular Ultrasound and Virtual Histology of Basilar Artery Atherosclerotic Lesion

    PubMed Central

    López-Rueda, A.; González García, A.; Aguilar Pérez, M.; Gutiérrez Jarrín, R.K.; Mayol Deyá, A.

    2011-01-01

    Summary To our knowledge, this paper presents the first intravascular ultrasound and virtual histology (IVUS-VH) study in the basilar artery. IVUS-VH serves to characterize and determine the extension of the plaque and we also to check stent placement. PMID:22192552

  13. Dissecting Aneurysm of the Basilar Arterial Trunk Presenting with Pontine Infarction

    PubMed Central

    Jang, Y.-G.; Ryu, C.W.; Kim, J.S.; Cha, E.Y.; Pyun, H.W.; Kim, D.Y.; Choi, J.W.; suh, D.C.

    2007-01-01

    Summary Dissecting basilar aneurysms have rarely been reported but are associated with high morbidity and mortality. Therefore, controversy exists as to the proper management of such lesions because their natural course is not well understood. We describe a 50-year-old man with a dissecting aneurysm involving the lower basilar trunk who presented with pontine infarction corresponding to the aneurysmal sac location. We obliterated the dissecting basilar aneurysm by coil embolization of the aneurysmal sac as well as the diseased segment of the basilar trunk after confirmation of collateral filling of the basilar artery through the posterior communicating artery. The patient recovered without any procedural complication. Eight month follow-up revealed complete disappearance of the aneurysm without symptom recurrence together with preservation of collateral flow in the distal basilar artery. Obliteration of the parent artery as well as the aneurysmal sac with coils could be considered in a lower basilar aneurysm of a dissecting nature. PMID:20566107

  14. Estrogen withdrawal selectively increases serotonin reactivity in rabbit basilar artery.

    PubMed

    Shay, J; Futo, J; Badrov, N; Moss, J

    1994-01-01

    Clinical observations and laboratory investigations suggest that gender and menstrual status modulate cerebrovascular reactivity. We prepared 7 groups of rabbits (I) males (II) oophorectomized untreated females, (III) testosterone treated oophorectomized females, (IV) superovulated females, (V) superovulated estrogen withdrawn females, (VI) estrogen treated oophorectomized females, and (VII) estrogen withdrawn females to mimic phases of the estrous cycle and compare cerebral basilar artery reactivity to serotonin (5-HT) and norepinephrine (NE) in vitro. Basilar artery sensitivity to 5-HT vasoconstriction was increased in oophorectomized, acutely estrogen withdrawn females (Group VII) when compared to estrogen maintained and the other groups (p < 0.0001). There was a significant reduction in 5-HT sensitivity in superovulated females (Group IV) (p < 0.001). The change in 5-HT sensitivity is selective and was not observed for NE. Nitroarginine treatment and mechanical denudement resulted in higher Tmax and lower ED50 for both NE and 5-HT regardless of hormonal manipulation. We conclude that estrogen withdrawal increases 5-HT vasoreactivity by an endothelium independent mechanism. PMID:8084212

  15. Inhibitory effect of 4-aminopyridine on responses of the basilar artery to nitric oxide

    PubMed Central

    Sobey, Christopher G; Faraci, Frank M

    1999-01-01

    Voltage-dependent K+ channels are present in cerebral arteries and may modulate vascular tone. We used 200 μM 4-aminopyridine (4-AP), thought to be a relatively selective inhibitor of voltage-dependent K+ channels at this concentration, to test whether activation of these channels may influence baseline diameter of the basilar artery and dilator responses to nitric oxide (NO) and cyclic GMP in vivo. Using a cranial window in anaesthetized rats, topical application of 4-AP to the basilar artery (baseline diameter=240±5 μm, mean±s.e.mean) produced 10±1% constriction. Sodium nitroprusside (a NO donor), acetylcholine (which stimulates endothelial release of NO), 8-bromo cyclic GMP (a cyclic GMP analogue), cromakalim (an activator of ATP-sensitive K+ channels) and papaverine (a non-NO, non-K+ channel-related vasodilator) produced concentration-dependent vasodilator responses that were reproducible. Responses to 10 and 100 nM nitroprusside were inhibited by 4-AP (20±4 vs 8±2% and 51±5 vs 33±5%, respectively, n=10; P<0.05). Responses to acetylcholine and 8-bromo cyclic GMP were also partially inhibited by 4-AP. In contrast, 4-AP had no effect on vasodilator responses to cromakalim or papaverine. These findings suggest that NO/cyclic GMP-induced dilator responses of the basilar artery are selectively inhibited by 4-aminopyridine. Responses to nitroprusside were also markedly inhibited by 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylate cyclase; 16±4 vs 1±1% and 44±7 vs 7±1%; n=10; P<0.05). Thus, dilator responses of the rat basilar artery to NO appear to be mediated by activation of soluble guanylate cyclase and partially by activation of a 4-aminopyridine-sensitive mechanism. The most likely mechanism would appear to be activation of voltage-dependent K+ channels by NO/cyclic GMP. PMID:10217538

  16. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.

    PubMed

    Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y; Lua, Ahai Chang; Lee, Tony Jer-Fu

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation

  17. Model studies of blood flow in basilar artery with 3D laser Doppler anemometer

    NASA Astrophysics Data System (ADS)

    Frolov, S. V.; Sindeev, S. V.; Liepsch, D.; Balasso, A.; Proskurin, S. G.; Potlov, A. Y.

    2015-03-01

    It is proposed an integrated approach to the study of basilar artery blood flow using 3D laser Doppler anemometer for identifying the causes of the formation and development of cerebral aneurysms. Feature of the work is the combined usage of both mathematical modeling and experimental methods. Described the experimental setup and the method of measurement of basilar artery blood flow, carried out in an interdisciplinary laboratory of Hospital Rechts der Isar of Technical University of Munich. The experimental setup used to simulate the blood flow in the basilar artery and to measure blood flow characteristics using 3D laser Doppler anemometer (3D LDA). Described a method of numerical studies carried out in Tambov State Technical University and the Bakoulev Center for Cardiovascular Surgery. Proposed an approach for sharing experimental and numerical methods of research to identify the causes of the basilar artery aneurysms.

  18. High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function.

    PubMed

    Toklu, H Z; Muller-Delp, J; Sakaraya, Y; Oktay, S; Kirichenko, N; Matheny, M; Carter, C S; Morgan, D; Strehler, K Y E; Tumer, N; Scarpace, P J

    2016-04-01

    The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function. PMID:27226180

  19. Chronic supplementation of paeonol combined with danshensu for the improvement of vascular reactivity in the cerebral basilar artery of diabetic rats.

    PubMed

    Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

    2012-01-01

    One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl(2)-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic

  20. Traumatic basilar artery entrapment with patency of pontine perforators and absence of significant brainstem infarction: report of an unusual case.

    PubMed

    Kliesch, Stefan; Bauknecht, Christian; Bohner, Georg; Liebig, Thomas; Siebert, Eberhard

    2016-01-01

    We report a rare case of entrapment of the basilar artery into the sphenoid bone caused by a longitudinal fracture of the clivus. Using high resolution three-dimensional flat panel angiography, we show preservation of the basilar artery perforators in spite of severe stenosis of the entrapped segment of the basilar artery. There were no obvious signs and symptoms of posterior fossa stroke clinically or radiographically as far as could be assessed under given clinical circumstances. PMID:27646318

  1. Aneurysms of the fenestrated basilar artery treated with Gulielmi Detachabe Coils: case report.

    PubMed

    Luo, C B; Chang, F C; Teng, M M; Liring, J F; Chen, S S

    2001-01-01

    Multiple aneurysms at the site of a basilar artery fenestration (BAF) are extremely rare. We report a case of BAF in association with two aneurysms successfully treated with Guglielmi Detachable Coils (GDCs). A 42-year-old male presented with subarachnoid hemorrhage and consciousness change. Angiograms of the vertebrobasilar artery demonstrated fenestration of the proximal basilar artery associated with two aneurysms. Embolization of aneurysms was done by using GDCs. Aneurysms were almost completely obliterated with preservation of the flow and lumen of the vertebrobasilar system. The patient remains asymptomatic at clinical follow-up of 18 months.

  2. Role of L-type Ca(2+) channels, sarcoplasmic reticulum and Rho kinase in rat basilar artery contractile properties in a new model of subarachnoid hemorrhage.

    PubMed

    Egea-Guerrero, Juan José; Murillo-Cabezas, Francisco; Muñoz-Sánchez, María Ángeles; Vilches-Arenas, Angel; Porras-González, Cristina; Castellano, Antonio; Ureña, Juan; González-Montelongo, María del Carmen

    2015-09-01

    We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery. A significant increase of basal tone, measured 4 and 60min after normalization, was observed on day 5 after SAH and at 60min on days 2 and 3 after SAH. This phenomenon was suppressed with LTCCs and ROCK inhibitors. We have also studied arterial rings vasoreactivity in response to high K(+) solutions. Interestingly, there were no significant differences in the phasic component of the high K(+)-induced contraction between sham and SAH groups, whereas a significant increase in the sustained contraction was observed on day 5 after SAH. This latter component was sensitive to fasudil, and selectively reduced by low nifedipine concentration, and phospholipase C and SR-ATPase inhibitors. Therefore, our data suggest that the metabotropic function of LTCCs is potentiated in SAH. Our results could provide a new strategy to optimize the pharmacological treatment of this pathological process.

  3. Rapid ventricular pacing for a basilar artery pseudoaneurysm in a pediatric patient: case report.

    PubMed

    Nimjee, Shahid M; Smith, Tony P; Kanter, Ronald J; Ames, Warwick; Machovec, Kelly A; Grant, Gerald A; Zomorodi, Ali R

    2015-06-01

    Large cerebral aneurysms of the basilar apex are difficult to treat. Recently, endovascular treatment has mitigated much of the morbidity associated with treating these lesions. However, the morphology of aneurysms of the vertebrobasilar system can preclude endovascular treatment. Rapid ventricular pacing (RVP) facilitates open surgical treatment of cerebral aneurysms. It can assist in reducing the pressure of the neck of the aneurysm, allowing safe application of a clip. The authors present a case of a pediatric patient who developed a basilar artery pseudoaneurysm that required surgery. Given the large size of the aneurysm, RVP was performed, allowing the surgeons to dissect the dome of the aneurysm from the surrounding tissue and pontine perforating branches away from the lesion to safely clip the lesion. The patient had an uneventful recovery. To the authors' knowledge, this represents the first known case of RVP to aid in basilar artery clip occlusion in a pediatric patient.

  4. Numerical simulations of post-surgical flow and thrombosis in basilar artery aneurysms

    NASA Astrophysics Data System (ADS)

    Seshadhri, Santhosh; Lawton, Michael; Boussel, Loic; Saloner, David; Rayz, Vitaliy

    2015-11-01

    Surgical treatment of basilar artery aneurysms presents a major challenge since it is crucial to preserve the flow to the vital brainstem perforators branching of the basilar artery. In some cases, basilar aneurysms can be treated by clipping vessels in order to induce flow reduction and aneurysm thrombosis. Patient-specific CFD models can provide guidance to clinicians by simulating postoperative flows resulting from alternative surgeries. Several surgical options were evaluated for four basilar aneurysm patients. Patient-specific models were generated from preoperative MR angiography and MR velocimetry data and modified to simulate different procedures. The Navier-Stokes equations were solved with a finite-volume solver Fluent. Virtual contrast injections were simulated by solving the advection-diffusion equation in order to estimate the flow residence time and determine thrombus-prone regions. The results indicated on procedures that reduce intra-aneurysmal velocities and flow regions which are likely to become thrombosed. Thus CFD modeling can help improve the outcome of surgeries altering the flow in basilar aneurysms.

  5. Evaluation of prostaglandin biosynthetic activity in canine basilar artery following subarachnoid injection of blood.

    PubMed

    Sasaki, T; Murota, S I; Wakai, S; Asano, T; Sano, K

    1981-11-01

    Transformation of arachidonic acid into prostaglandins was investigated in the basilar artery by incubating sections of artery with carbon-14-labeled arachidonic acid. Thin-layer radiochromatography revealed that, in normal canine basilar arteries, 14C-arachidonic acid was transformed mainly to 6-keto-prostaglandin (PG)F1 alpha, a spontaneous metabolite of prostacyclin (PGI2). Among other prostaglandins, only a small amount of PGF2 alpha was detected, whereas PGD2, PGE2, and thromboxane B2 were not. Arteries removed on Days 3 and 8 after subarachnoid blood injection showed a prostaglandin synthesis profile similar to that in the normal cerebral artery. In borate-buffered saline (0.1M borate buffer, pH 9.0/0.15M NaCl = 1:9, vol/vol), canine basilar artery produced a PGI2-like substance that inhibited adenosine diphosphate (ADP)-induced platelet aggregation. Its anti-aggregatory activity was completely abolished by acidification. Aspirin likewise inhibited production of the anti-aggregatory substance. From these results, it was concluded that the anti-aggregatory activity was due solely to the production of PGI2 by the arterial specimen. Based on the above results, PGI2 biosynthetic activity in the cerebral artery exposed to subarachnoid blood injection was bioassayed by measuring the inhibitory activity of the incubation product upon ADP-induced platelet aggregation following incubation of the arteries in borate-buffered saline for 5 to 30 minutes at 20 degrees C, using synthetic PGI2-Na as a standard. The synthetic activity of PGI2 in the artery exposed to subarachnoid blood injection had diminished remarkably by Days 3 and 8. This diminution of PGI2 synthesis in the cerebral artery may be involved in the pathogenesis of cerebral vasospasm.

  6. Study on the correlation of vertebral artery dominance, basilar artery curvature and posterior circulation infarction.

    PubMed

    Zhu, Wei; Wang, Ya-Fang; Dong, Xiao-Feng; Feng, Hong-Xuan; Zhao, He-Qing; Liu, Chun-Feng

    2016-09-01

    Vertebral artery dominance (VAD), which is a common congenital variation of vertebral artery, may be associated with an increased risk of cerebral posterior circulation infarction (PCI). The aims of this study were to investigate the correlation of VAD with incidence and laterality of PCI, and oblige the correlation of VAD and basilar artery (BA) curvature. Incidence of separate territory infarction in posterior circulation and incidence of BA curvature were compared between 78 VAD patients and 68 controls. VA dominance, laterality of BA curvature and separate territory infarction, and their directional relationships were observed in VAD group. The incidence of BA curvature in VAD group was significantly higher than that in controls (P = 0.000). 89.7 % (35/39) of patients had an opposite directional relationship between dominant VA and BA curvature. The total incidence of PCI in VAD group was significantly higher than that in controls (P = 0.001). The incidences of posterior inferior cerebellar artery (PICA) and BA territory infarction were both significantly higher than those in controls [11.5 % (9/78) vs. 1.5 % (1/68), P = 0.016; 20.5 % (16/78) vs. 7.4 % (5/68), P = 0.024]. No differences were found in superior cerebellar artery and posterior cerebral artery territory infarction between two groups. 77.8 % (7/9) of PICA infarction were on the opposite side of dominant VA. 75.0 % (12/16) of BA infarction were on the side of dominant VA. The incidence of PCI in BA curvature patients was significantly higher than that in BA straight patients. The incidence of BA curvature is higher in VAD patients, and BA usually bends to the opposite side of dominant VA. The incidence of PCI is higher in VAD patients, especially in PICA infarction and BA infarction patients.

  7. Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH.

    PubMed

    Sun, Li; Li, Qin; Wang, Wei-Ting; Chen, Yu-Hua; Guo, Lian-Jun

    2015-04-01

    1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10(-5) M) also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue. PMID:26170819

  8. Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts

    PubMed Central

    Hong, J M; Chung, C-S; Bang, O Y; Yong, S W; Joo, I S; Huh, K

    2009-01-01

    Objectives: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. Methods: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The “dominant” VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. Results: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). Conclusions: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts. PMID:19414436

  9. Characterization of the 5-hydroxytryptamine receptor which mediates contraction of the human isolated basilar artery.

    PubMed

    Parsons, A A; Whalley, E T

    1989-01-01

    This paper reports part of a study which investigated the identity of the receptor involved in 5-hydroxytryptamine (5-HT) mediated contraction of the human basilar artery in vitro. 5-HT and a variety of 5-HT receptor agonists contracted human isolated basilar artery with a rank order of agonist potency: 5-carboxamidotryptamine greater than 5-HT greater than GR43175 much much greater than 2-methyl-5-HT. The maximum response produced by these agonists differed. The contractile responses to both 5-HT and GR43175 were resistant to antagonism by the 5-HT2 antagonist ketanserin and the 5-HT3 antagonist GR38032, indicating that neither 5-HT nor GR43175 activate 5-HT2 and 5-HT3 receptors in this tissue. In striking contrast, methiothepin (an antagonist at 5-HT1-like receptors) proved a potent antagonist of the contractile actions of both 5-HT and GR43175. Methiothepin did not antagonize the contractile response to the thromboxane-A2 mimetic U-46619. It is concluded that 5-HT and GR43175 contract the human isolated basilar artery by activating 5-HT1-like receptors. It is suggested that the antimigraine action of GR43175 may reflect its ability to constrict certain cranial arteries via 5-HT1-like receptor activation. PMID:2544283

  10. Acute Pontine Infarction due to Basilar Artery Dissection from Strenuous Physical Effort: One from Sexual Intercourse and Another from Defecation

    PubMed Central

    Kim, Su-Ho; Suh, Sang-Jun; Lee, Jeong-Ho; Ryu, Kee-Young; Kang, Dong-Gee

    2016-01-01

    A basilar artery dissection (BAD) is an extremely rare disease. It can lead to hemorrhage or infarction involving the brain stem, and is often associated with grave outcome. However, little is known about the pathophysiology of BAD, and its proper managements are yet in controversy. Herein, we report on two rare cases of basilar artery dissection from strenuous physical effort; one from sexual intercourse and another from defecation. The treatment modalities and the outcomes are also discussed. PMID:27790399

  11. Very late in-stent thrombosis 9 years after double stent treatment of fusiform basilar artery aneurysm.

    PubMed

    Juszkat, Robert; Stanislawska, Katarzyna; Wasik, Norbert; Jankowski, Roman; Liebert, Włodzimierz

    2015-06-01

    Endovascular treatment seems to be the best approach to posterior circulation fusiform aneurysms. Double stent techniques are frequently used to occlude basilar artery dilations. Unfortunately, there is a limited number of studies that have followed up with patients over prolonged periods of time in order to evaluate delayed complications, such as stenosis, thrombosis or migration of stents. We present an unusual case of in-stent thrombosis 9 years after basilar artery aneurysm treatment to caution about complications associated with double stent implantation.

  12. The use of mechanical thrombectomy in the treatment of basilar artery occlusion--case report.

    PubMed

    Knap, Daniel; Honkowicz, Maciej; Kirmes, Tomasz; Koroński, Marcin; Kysiak, Marzena; Bukański, Mateusz; Sieroń, Dominik; Dymon, Izabela; Baron, Jan

    2015-01-01

    Occlusion of the basilar artery (BAO) is a rare cause of stroke, making up approximately 1% of all cases. Ischemic stroke within the basilar artery is associated with serious complications and high mortality (75-91%). BAO may occur initially in the form of mild prodromal symptoms with neurological disorders, the consequences of which can lead to death. For these reasons, BAO requires rapid diagnosis and treatment. We report the case of a 26-year-old man who suffered basilar artery occlusion and was treated with endovascular therapy. The patient was disqualified from intra-venous thrombolysis and endovascular treatment due to exceeding the therapeutic time window. Despite this, due to the location of ischemia and age of the patient, it was decided to proceed with a mechanical thrombectomy (TM). Vessel patency was restored using the Solitaire FR stent. Treatment continued with antiplatelet therapy. Despite a significant overshoot of the time window the procedure was successful and complete recanalization was achieved. During hospitalization, significant neurological symptom reductions were observed. There is no accurate data on which method of treatment of ischemic stroke is best for BAO. Expectations about the effectiveness of endovascular techniques are high.

  13. The challenge of basilar artery occlusion wake-up stroke: too late for intravenous thrombolysis?

    PubMed

    Caliandro, Pietro; Reale, Giuseppe; Tartaglione, Tommaso; Rossini, Paolo Maria

    2016-07-01

    We describe the case of a patient carried to our emergency department, with the wake-up finding of dysarthria, right hemiplegia and worsening consciousness impairment (NIHSS 12). After performing a CT angiography, which showed complete basilar occlusion, we determined the MR DWI-FLAIR mismatch to estimate the stroke onset time. Because of the favorable mismatch (DWI hyperintensity in the left pons, no FLAIR hyperintensity in the same region), the patient underwent thrombolysis with sudden neurological improvement. In addition, the DWI hyperintensity first observed in the left pons totally regressed after thrombolysis. Wake-up stroke constitutes about 14 % of all strokes, while the percentage of basilar artery occlusion wake-up strokes is still unknown. Although thrombolysis in patients with unknown-onset time is still an off-label therapy, basilar artery occlusion is a potentially fatal event. In our case we used RM DWI-FLAIR mismatch to rapidly estimate the stroke onset time and to treat the patient with an off-label but potentially effective and safe therapy.

  14. Endothelin-1 and endothelin receptors in the basilar artery of the capybara.

    PubMed

    Loesch, Andrzej; Gajkowska, Barbara; Dashwood, Michael R; Fioretto, Emerson T; Gagliardo, Karina M; Lima, Ana R De; Ribeiro, Antonio A C M

    2005-02-01

    Little is known about cerebral vasculature of capybara, which seems may serve as a natural model of studying changes in cerebral circulation due to internal carotid artery atrophy at animal sexual maturation. This is the first study of the light- and electron-immunocytochemical localisation of endothelin-1 (ET-1) and ETA and ETB endothelin receptors in the basilar artery of capybaras (6 to 12-month-old females and males) using an ExtrAvidin detection method. All animals examined showed similar patterns of immunoreactivity. Immunoreactivity for ET-1 was detected in the endothelium and adventitial fibroblasts, whilst immunoreactivity for ETA and ETB receptors was present in the endothelium, vascular smooth muscle, perivascular nerves and fibroblasts. In endothelial cells immunoreactivity to ET-1 was pronounced in the cytoplasm or on the granular endoplasmic reticulum. Similar patterns of immunolabelling were observed for ETA and ETB receptors, though cytoplasmic location of clusters of immunoprecipitate seems dominant. These results suggest that the endothelin system is present throughout the wall of the basilar artery of capybara.

  15. Very late in-stent thrombosis 9 years after double stent treatment of fusiform basilar artery aneurysm

    PubMed Central

    Juszkat, Robert; Stanislawska, Katarzyna; Jankowski, Roman; Liebert, Włodzimierz

    2015-01-01

    Endovascular treatment seems to be the best approach to posterior circulation fusiform aneurysms. Double stent techniques are frequently used to occlude basilar artery dilations. Unfortunately, there is a limited number of studies that have followed up with patients over prolonged periods of time in order to evaluate delayed complications, such as stenosis, thrombosis or migration of stents. We present an unusual case of in-stent thrombosis 9 years after basilar artery aneurysm treatment to caution about complications associated with double stent implantation. PMID:25964437

  16. Dolichoectasia of the vertebral basilar and internal carotid arteries: A case report and literature review

    PubMed Central

    Yuh, Sung-Joo; Alkherayf, Fahad; Lesiuk, Howard

    2013-01-01

    Background: Dolichoectasia is a rare disorder of the cerebral vasculature consisting of vascular elongation, widening, and tortuosity, usually involving the vertebral and basilar arteries. Its neurological symptoms and signs are highly variable. Case Description: We present a case of dolichoectasia of the vertebrobasilar system in a patient with a long standing history of multiple falls. Repeat neuroimaging revealed an increase in size of the dolichoectatic segment. In addition, a new fusiform dilatation of the contralateral petrous segment of the internal carotid artery and isolated ventriculomegaly had developed. Conclusion: Vertebrobasilar dolichoectasia can cause multiple clinical manifestations, with hydrocephalus being less common. In addition, having dolichoectasia of both posterior and anterior circulation is extremely rare. PMID:24381796

  17. Assessment of Basilar Artery Reactivity in Stroke and Subarachnoid Hemorrhage Using Wire Myograph.

    PubMed

    Ghantous, Crystal M; Azrak, Zeina; Rahman, Farah Abdel; Itani, Hana A; Zeidan, Asad

    2016-01-01

    Blood flow regulation of normal cerebral arteries is a critical and important factor to supply the brain tissue with nutrients and oxygen. Stroke insult results in a disruption or reduction in cerebral arteries' blood flow with subsequent brain tissue damage. Hemorrhagic stroke is one type of stroke and accounts for about 13 % of all of stroke insults. In this type of stroke, the cerebral artery breaks open and causes bleeding in or surrounding the brain. Subsequently, this bleeding causes blood vessels to constrict in a process called vasospasm, in which the vessels narrow and impede the blood flow to brain tissue. Hemorrhagic stroke is the major cause of prolonged constriction of cerebral arteries. This leads to partial brain damage and sometimes death in patients with aneurysmal subarachnoid hemorrhage. Among the key delicate techniques to assess small blood vessel functionality is the wire myograph, which can be utilized in several cerebral injury models including stroke. The wire myograph is a device that provides information about the reactivity, stiffness, and elasticity of small blood vessels under isometric conditions. In this book chapter, we describe the techniques involved in wire myography assessment and the different measures and parameters recorded; we describe the utility of this technique in evaluating the effects of subarachnoid hemorrhage on basilar artery sensitivity to different agonists. PMID:27604742

  18. Successful coil embolization of a ruptured basilar artery aneurysm in a child with leukemia: a case report.

    PubMed

    Hayashi, Shihori; Maehara, Taketoshi; Mukawa, Maki; Aoyagi, Masaru; Yoshino, Yoshikazu; Nemoto, Shigeru; Ono, Toshiaki; Ohno, Kikuo

    2014-01-01

    Ruptured intracranial aneurysms are rare in the pediatric population compared to adults. This has incited considerable discussion on how to treat children with this condition. Here, we report a child with a ruptured saccular basilar artery aneurysm that was successfully treated with coil embolization. A 12-year-old boy with acute lymphoblastic leukemia and accompanying abdominal candidiasis after chemotherapy suddenly complained of a severe headache and suffered consciousness disturbance moments later. Computed tomography scans and cerebral angiography demonstrated acute hydrocephalus and subarachnoid hemorrhage caused by saccular basilar artery aneurysm rupture. External ventricular drainage was performed immediately. Because the patient was in severe condition and did not show remarkable signs of central nervous system infection in cerebrospinal fluid studies, we applied endovascular treatment for the ruptured saccular basilar artery aneurysm, which was successfully occluded with coils. The patient recovered without new neurological deficits after ventriculoperitoneal shunting. Recent reports indicate that both endovascular and microsurgical techniques can be used to effectively treat ruptured cerebral aneurysms in pediatric patients. A minimally invasive endovascular treatment was effective in the present case, but long-term follow-up will be necessary to confirm the efficiency of endovascular treatment for children with ruptured saccular basilar artery aneurysms.

  19. Stent-assisted Coiling for Ruptured Basilar Artery Dissecting Aneurysms: An Initial Experience of Four Cases

    PubMed Central

    KOIZUMI, Satoshi; SHOJIMA, Masaaki; IIJIMA, Akira; OYA, Soichi; MATSUI, Toru; YOSHIKAWA, Gakushi; TSUTSUMI, Kazuo; NAKATOMI, Hirofumi; SAITO, Nobuhito

    2016-01-01

    No treatment strategy has been established for subarachnoid hemorrhages due to basilar artery (BA) trunk dissecting aneurysms. Our aim was to report our initial experience performing stent-assisted coiling (SAC) for ruptured BA dissecting aneurysms to validate the effectiveness of this treatment. We experienced four consecutive cases of ruptured dissecting BA trunk aneurysm treated with SAC between 2008 and 2014 at three institutions. Aneurysm rebleeding was prevented without causing severe brainstem ischemia in all cases. In our opinion, both the blockage of the inflow to aneurysms and the preservation of the antegrade flow of the BA can be achieved by SAC, although controversies regarding long-term stability and appropriate antiplatelet therapy remain. PMID:26667082

  20. Transient basilar artery occlusion monitored by transcranial color Doppler presenting with a spectacular shrinking deficit: a case report

    PubMed Central

    2010-01-01

    Introduction We describe the case of a 79-year-old Caucasian Italian woman with a transient basilar occlusion monitored by transcranial Doppler, with subsequent recanalization and clinical shrinking deficit. This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. This case is important and needs to be reported because transient basilar occlusion may be easily diagnosed if transcranial Doppler is performed. Case presentation A 79-year-old woman affected by chronic atrial fibrillation and not treated with oral anticoagulants, cardioverted to sinus rhythm during a gastric endoscopy. She then showed a sudden-onset loss of consciousness, horizontal and vertical gaze palsy, tetraparesis and bilateral miosis and coma. Two hours later, the symptoms resolved quickly, leaving no residual neurologic deficits. Transcranial Doppler examination showed a dampened flow in the basilar artery in the emergency examination and a restored flow when the symptoms resolved. Conclusion This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. We believe that transcranial Doppler should be performed in all cases of unexplained acute loss of consciousness, in particular, if associated with signs of brainstem dysfunctions. PMID:20205759

  1. Dolichoectasia of the circle of Willis arteries and fusiform aneurysm of basilar artery – case report and review of the literature

    PubMed Central

    Baran, Bogusława; Kornafel, Olga; Guziński, Maciej; Sąsiadek, Marek

    2012-01-01

    Summary Background: Dolichoectasia of intracranial arteries is a rare arteriopathy characterized by elongation and widening of the arteries and disturbance of the laminar blood flow. It involves mostly vertebral and basilar arteries. In advanced cases, formation of a fusiform aneurysm is possible. Case Report: A sixty-four-year-old female with hypertension was admitted to the hospital with severe non-systemic vertigo and dysarthria, which had lasted for a couple of weeks. Imaging of the brain revealed dolichoectasia of arteries of the circle of Willis coexisting with a fusiform aneurysm of the basilar artery. Conclusions: Intracranial arterial dolichoectasia may be asymptomatic for a long time. However, in many cases it leads to neurological symptoms associated with haemodynamic disturbance (due to unstable wall clots) and mass effect caused by the widened vessel. PMID:22844310

  2. Endovascular mechanical thrombectomy in basilar artery occlusion: variables affecting recanalization and outcome.

    PubMed

    Gilberti, Nicola; Gamba, Massimo; Premi, Enrico; Costa, Angelo; Vergani, Veronica; Delrio, Ilenia; Spezi, Raffaella; Mardighian, Dikran; Frigerio, Michele; Gasparotti, Roberto; Padovani, Alessandro; Magoni, Mauro

    2016-04-01

    Ischemic stroke due to basilar artery occlusion (BAO) is frequently associated with a poor prognosis. To date the most effective therapeutic approach has not been established and little is known about the predictors of clinical outcome. The aim of this study was to describe safety and efficacy of intra-arterial mechanical thrombectomy (IAMT) through latest generation devices in patients with BAO, focusing on those variables that may affect recanalization and clinical outcome. We analyzed retrospectively a series of 32 patients with BAO who underwent IAMT. We assessed the association of some clinical and neuroradiological features with recanalization rate and clinical outcome. Successful recanalization was achieved in 28 out of 32 patients (87.5 %). Symptomatic intracerebral hemorrhage (SICH) was observed in 2/32 patients (6.3 %) and mortality in the first 3 months was 25.0 %. At 3-month follow up evaluation, 13/32 patients (40.6 %) showed a good functional outcome (mRS score ≤2). There were no statistical differences in term of age, gender, risk factors, cause of stroke, recanalization rate, pre-treatment pc-ASPECTS score and SICH frequencies between patients with favorable and unfavorable outcome. Increased length of thrombi was associated with unfavorable clinical outcome at 3 months. Recanalization rate was not affected by any of the variables considered. In BAO, IAMT through newest generation devices has high recanalization rates and low complication frequencies. Length of BAO is an important predictor of clinical outcome.

  3. A Comparison between Mechanical Thrombectomy and Intra-arterial Fibrinolysis in Acute Basilar Artery Occlusion: Single Center Experiences

    PubMed Central

    Jung, Seunguk; Jung, Cheolkyu; Bae, Yun Jung; Choi, Byung Se; Kim, Jae Hyoung; Lee, Sang-Hwa; Chang, Jun Young; Kim, Beom Joon; Han, Moon-Ku; Bae, Hee-Joon; Kwon, Bae Ju; Cha, Sang-Hoon

    2016-01-01

    Background and Purpose Recent advances in intra-arterial techniques and thrombectomy devices lead to high rate of recanalization. However, little is known regarding the effect of the evolvement of endovascular revascularization therapy (ERT) in acute basilar artery occlusion (BAO). We compared the outcome of endovascular mechanical thrombectomy (EMT) versus intra-arterial fibrinolysis (IAF)-based ERT in patients with acute BAO. Methods After retrospectively reviewed a registry of consecutive patients with acute ischemic stroke who underwent ERT from September 2003 to February 2015, 57 patients with acute BAO within 12 hours from stroke onset were enrolled. They were categorized as an IAF group (n=24) and EMT group (n=33) according to the primary technical option. We compared the procedural and clinical outcomes between the groups. Results The time from groin puncture to recanalization was significantly shorter in the EMT group than in the IAF group (48.5 [25.3 to 87.8] vs. 92 [44 to 179] minutes; P=0.02) The rate of complete recanalization was significantly higher in the EMT group than in the IAF group (87.9% vs 41.7%; P<0.01). The good outcome of the modified Rankin Scale score≤2 at 3 months was more frequent in the EMT group than in the IAF group, but it was not statistically significant (39.4% vs 16.7%; P=0.06). Conclusions EMT-based ERT in patients with acute BAO is superior to IAF-based ERT in terms of the reduction of time from groin puncture to recanalization and the improvement of the rate of complete recanalization. PMID:27283281

  4. Basilar artery dissection: A rare complication of posterior fossa epidermoid cyst resection, and evaluation of the possible effects of cerebrospinal fluid drainage on disease progression.

    PubMed

    Pikis, Stylianos; Cohen, José E; Margolin, Emil

    2016-10-01

    We report a rare case of a 45-year-old female with an unruptured basilar artery dissecting aneurysm presenting with locked-in syndrome due to brainstem ischemia eleven months following resection of a giant cerebellopontine angle epidermoid cyst and three months after insertion of ventriculo peritoneal shunt due to hydrocephalus. The etiology of basilar artery dissection and the effect of hydrocephalus and ventricular cerebrospinal fluid drainage on disease progression in this patient are unclear. Our report suggests a possible effect of hydrocephalus and ventricular cerebrospinal fluid drainage on intracranial arterial dissection progression. PMID:27344090

  5. Pb2+ inhibition of sympathetic alpha 7-nicotinic acetylcholine receptor-mediated nitrergic neurogenic dilation in porcine basilar arteries.

    PubMed

    Si, Min-Liang; Lee, Tony Jer-Fu

    2003-06-01

    Chronic exposure to inorganic lead (Pb2+) has been shown to facilitate peripheral vasoconstriction causing hypertension. Effect of lead on cerebral vascular function has not been reported. We have suggested in isolated porcine cerebral arteries that alpha 7-nicotinic acetylcholine receptors (alpha 7-nAChRs) on perivascular sympathetic nerves mediate calcium influx in these neurons, resulting in release of norepinephrine. The released norepinephrine then acts on presynaptic beta2-adrenoceptors located on the neighboring nitrergic nerve terminals, causing nitric oxide (NO) release and vasodilation. Because Pb2+ has been shown to inhibit alpha 7-nAChR-mediated responses in the central nervous system, effects of Pb2+ on alpha 7-nAChR-mediated nitrergic neurogenic dilation in isolated porcine basilar arteries and calcium influx in cultured superior cervical ganglion (SCG) cells of the pig were examined using in vitro tissue bath and confocal microscopic techniques. The results indicated that Pb2+ (but not Cd2+, Zn2+, or Al3+) in a concentration-dependent manner blocked relaxation of endothelium-denuded basilar arterial rings induced by nicotine (100 microM) and choline (1 mM) without affecting relaxation induced by sodium nitroprusside or isoproterenol. Furthermore, significant calcium influx in cultured SCG cells induced by choline and nicotine was attenuated specifically by Pb2+ with IC50 values comparable with those from tissue bath study. These results provide evidence supporting that lead is a likely antagonist for alpha 7-nAChRs that are found on postganglionic sympathetic adrenergic nerve terminals of SCG origin. Furthermore, these results indicate that lead can attenuate dilation of cerebral arteries by blocking sympathetic nerve-mediated release of NO from the perivascular nitrergic nerves.

  6. Differential effects of acetylcholine, nitric oxide and levcromakalim on smooth muscle membrane potential and tone in the rabbit basilar artery.

    PubMed

    Plane, F; Garland, C J

    1993-10-01

    1. Endothelium-dependent hyperpolarization of smooth muscle cells in isolated, pre-contracted segments of rabbit basilar artery in response to acetylcholine (100 microM) was abolished in the presence of glibenclamide (10 microM). 2. Acetylcholine-evoked relaxation was unaffected by either glibenclamide or 65 mM potassium chloride, indicating that the change in membrane potential did not form an essential component of relaxation and that high concentrations of potassium did not inhibit the release or action of endothelium-derived relaxing factor in this vessel. 3. Saturated solutions of nitric oxide (NO) gas in solution (150 microM), which evoked maximal relaxation of arterial segments pre-contracted and depolarized by noradrenaline (10-100 microM), did not alter the membrane potential of either unstimulated or depolarized smooth muscle cells. 4. The potassium channel opener levcromakalim, evoked concentration-dependent relaxation and hyperpolarization in pre-constricted smooth muscle cells. The threshold concentrations for hyperpolarization and relaxation, the EC50 values and the maximally effective concentration of levcromakalim (around 30 nM, 150 nM and 10 microM, respectively) were not significantly different, and both components of the response were inhibited by glibenclamide (10 microM), indicating a close coupling between the two responses. 5. In the presence of 65 mM potassium chloride, the hyperpolarization to levcromakalim was abolished, while a small relaxation (25 +/- 4%) persisted, indicating an additional mechanism for relaxation to this agent. 6. These results show that different mechanisms underlie the relaxant action of potassium channel openers, NO and endothelium-derived factors in cerebral arteries and provide further evidence that in the basilar artery, in contrast to some other vessels, endothelium-dependent hyperpolarization to acetylcholine is not important for smooth muscle relaxation.

  7. Vanillin and vanillin analogs relax porcine coronary and basilar arteries by inhibiting L-type Ca2+ channels.

    PubMed

    Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

    2015-01-01

    Vanillin (VA) and vanillyl alcohol (VAA), components of natural vanilla, and ethyl vanillin (EtVA; synthetic analog) are used as flavoring agents and/or as additives by the food, cosmetic, or pharmaceutic industries. VA, VAA, and EtVA possess antioxidant and anti-inflammatory properties, but their vascular effects have not been determined. Therefore, we compared in isolated porcine coronary and basilar arteries the changes in isometric tension caused by VA, VAA, and EtVA. VA and its analogs caused concentration-dependent relaxations of both preparations during contractions from U46619 (9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α, a thromboxane A2 receptor agonist), and of coronary arteries contracted with KCl or endothelin-1. The order of potency was VAA < VA < EtVA. The relaxations were not inhibited by endothelium removal, by inhibitors of NO synthases (N(ω)-nitro-l-arginine methyl ester hydrochloride), cyclooxygenases (indomethacin), soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ]), KCa (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole [TRAM-34], 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-metheno-7H-dibenzo[b,n][1,5,12,16]tetraazacyclotricosine-5,13-diium ditrifluoroacetate hydrate [UCL-1684], or iberiotoxin), by KATP (glibenclamide), by Kir (BaCl2), by transient receptor potential receptor vanilloid 3 (TRPV3) channels (ruthenium red), or by antioxidants (catalase, apocynin, tempol, N-acetylcysteine, tiron). VA and its analogs inhibited contractions induced by Ca(2+) reintroduction in coronary arteries, and by an opener of L-type Ca(2+)-channels (methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate [Bay K8644]) in coronary and basilar arteries. They inhibited contractions of coronary rings induced by the protein kinase C activator phorbol 12,13-dibutyrate to the same extent as the removal of extracellular Ca(2+) or incubation with nifedipine. Thus, in porcine arteries

  8. Vanillin and vanillin analogs relax porcine coronary and basilar arteries by inhibiting L-type Ca2+ channels.

    PubMed

    Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

    2015-01-01

    Vanillin (VA) and vanillyl alcohol (VAA), components of natural vanilla, and ethyl vanillin (EtVA; synthetic analog) are used as flavoring agents and/or as additives by the food, cosmetic, or pharmaceutic industries. VA, VAA, and EtVA possess antioxidant and anti-inflammatory properties, but their vascular effects have not been determined. Therefore, we compared in isolated porcine coronary and basilar arteries the changes in isometric tension caused by VA, VAA, and EtVA. VA and its analogs caused concentration-dependent relaxations of both preparations during contractions from U46619 (9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α, a thromboxane A2 receptor agonist), and of coronary arteries contracted with KCl or endothelin-1. The order of potency was VAA < VA < EtVA. The relaxations were not inhibited by endothelium removal, by inhibitors of NO synthases (N(ω)-nitro-l-arginine methyl ester hydrochloride), cyclooxygenases (indomethacin), soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ]), KCa (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole [TRAM-34], 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-metheno-7H-dibenzo[b,n][1,5,12,16]tetraazacyclotricosine-5,13-diium ditrifluoroacetate hydrate [UCL-1684], or iberiotoxin), by KATP (glibenclamide), by Kir (BaCl2), by transient receptor potential receptor vanilloid 3 (TRPV3) channels (ruthenium red), or by antioxidants (catalase, apocynin, tempol, N-acetylcysteine, tiron). VA and its analogs inhibited contractions induced by Ca(2+) reintroduction in coronary arteries, and by an opener of L-type Ca(2+)-channels (methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate [Bay K8644]) in coronary and basilar arteries. They inhibited contractions of coronary rings induced by the protein kinase C activator phorbol 12,13-dibutyrate to the same extent as the removal of extracellular Ca(2+) or incubation with nifedipine. Thus, in porcine arteries

  9. Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

    PubMed Central

    Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-01-01

    We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke. PMID:27446523

  10. A conversion disorder or a stroke? A proximal basilar artery thrombosis induced 'locked-in' syndrome in a young Caucasian woman.

    PubMed

    Li, Wang; Brandon, Ohman; Smith, Debbie Villarreal; Petersen, Eric

    2013-03-14

    The incidence of the basilar artery occlusion is relatively low among all strokes. Clinical presentation varies depending on the location of the occlusion. The symptoms include mild dysarthria to coma or sudden death. The initial subtle clinical presentation could lead to misdiagnosis. Psychogenic diagnosis in the differential could make the timely diagnosis more difficult. This case involves a 34-year-old woman presenting with a gradual onset of slurred speech. The initial CT scan of head did not indicate any intracranial pathology, and she was initially treated for an anxiety/conversion disorder. With progression of the pathology, the patient quickly developed a 'locked-in' syndrome, with preserved high cognitive function and vertical eye movement, but otherwise total loss of motor function. The diagnosis was confirmed with MRI/MR angiography studies, which indicated thrombosis of the proximal basilar artery. Serological studies did not disclose any relevant risk factors.

  11. Role of potassium channels in the nitrergic nerve stimulation-induced vasodilatation in the guinea-pig isolated basilar artery

    PubMed Central

    Jiang, Fan; Li, Chun Guang; Rand, Michael J

    1998-01-01

    We studied the effects of various K+ channel blockers on the vasodilator responses of guinea-pig isolated basilar arteries to nitrergic nerve stimulation, the nitric oxide (NO) donor sodium nitroprusside (SNP), and the membrane permeable guanosine-3′, 5′-cyclic monophosphate (cyclic GMP) analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP).In endothelium-denuded preparations which were contracted with prostaglandin F2α (1 μM), electrical field stimulation (EFS, 10 Hz for 30 s) produced a vasodilatation which was totally blocked by the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester L-NAME; 100 μM) (n=3) and by the selective NO-sensitive guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 1 μM) (n=4). The vasodilator response to SNP (100 nM) was not reduced by L-NAME but was abolished by ODQ (1 μM) (n=4).EFS-elicited vasodilatation was partly but significantly reduced by the non-selective K+ channel blockers tetraethylammonium (TEA, 1 and 3 mM) and 4-aminopyridine (4-AP, 3 mM), and by the large-conductance calcium-activated K+ channel (KCa channel) blockers charybdotoxin (ChTX, 150 nM) and iberiotoxin (IbTX, 30 and 100 nM). In contrast, the ATP-sensitive K+ channel (KATP channel) blocker glibenclamide (1–10 μM) and the small-conductance KCa channel blocker apamin (100–500 nM) did not affect EFS-induced vasodilatation.The vasodilator response elicited by SNP (10–100 nM) was significantly reduced by TEA (3 mM) and ChTX (150 nM) but not by apamin (500 nM) or glibenclamide (1 μM). The vasodilatation elicited by 8-Br-cyclic GMP (100 μM) was also reduced by TEA (3 mM) and ChTX (150 nM).The results indicate that the vasodilatations induced by nitrergic nerve stimulation and the NO donor SNP in endothelium-denuded guinea-pig basilar artery depend on the formation of intracellular cyclic GMP. The increased cyclic GMP level activates large-conductance KCa channels which

  12. Resection of large epidermoid tumors ventral to the brainstem: techniques to expand the operative corridor across the basilar artery.

    PubMed

    Cohen-Gadol, Aaron A

    2014-01-01

    Epidermoid tumors comprise about 1% of all intracranial tumors. They are congenital lesions that arise from paramedian cisterns within the posterior fossa. These tumors present as heterogeneous hyperintense lesions on FLAIR and homogenous hyperintense lesions on DWI. Surgical resection remains the most accepted form of therapy, but epidermoid tumors may recur. These tumors are well exposed through a traditional retrosigmoid approach. The tumor can be removed relatively easily as it is avascular. However, the propensity of this tumor type to fill the small spaces within basal cisterns and attach to cranial nerves may make its complete resection challenging. Tumors resection has to preserve the surrounding arachnoid membranes encasing the cranial nerves. The author presents the case of a 42-year-old woman with a 1-year history of imbalance and nystagmus. An MRI revealed a large right-sided CP angle epidermoid tumor filling the ventral brainstem cistern and extending to the contralateral side, compressing the brainstem. The accompanying video illustrates resection of this mass through an extended (exposing the sigmoid sinus) retrosigmoid approach. The author removed the tumor piecemeal while protecting the cranial nerves. Small pieces of affected arachnoid covering the cranial nerves were not significantly manipulated. To excise the tumor along the contralateral paramedian cistern, the author used the space between the V and VII/VII cranial nerves to expose the space contralateral to the basilar artery and remove additional tumor. This maneuver allowed gross total resection of the tumor without a need to employ a more elaborate skull base approach such as petrosectomy. At 3-month follow-up visit after surgery, the patient's neurological exam returned to normal. The video can be found here: http://youtu.be/CzRb-GUvhog . PMID:24380510

  13. Mechanical thrombectomy with the Solitaire AB stent for treatment of acute basilar artery occlusion: A single-center experience.

    PubMed

    Du, Shiwei; Mao, Gengsheng; Li, Dongmei; Qiu, Ming; Nie, Qingbin; Zhu, Haibo; Yang, Yang; Zhang, Youping; Li, Youxiang; Wu, Zhongxue

    2016-10-01

    Basilar artery occlusion (BAO) remains one of the most devastating subtypes of ischemic stroke, and prognosis is poor if early recanalization is not achieved. The purpose of this study was to evaluate the safety and technical feasibility of mechanical thrombectomy with the Solitaire AB stent (Covidien, Irvine, CA, USA) for the treatment of acute BAO through a single-center experience. Twenty-one patients with acute BAO were treated with mechanical thrombectomy with the Solitaire AB stent device between 1st September 2011 and 1st December 2014. Recanalization was assessed using the Thrombolysis in Cerebral Infarction (TICI) scale system. Clinical outcome was established at discharge by The National Institute of Health Stroke Scale (NIHSS), and the mean time from symptom onset to recanalization determined. Authors had access to identifying information during or after data collection. The clinical status of patients on admission was severe, with a mean NIHSS score of 25.57±5.20 (range: 16-38), and the number of patients with TICI 2b or 3 was 0. The mean time from symptom onset to recanalization was 579.00±188.78min (range: 360-960min). At 3-month follow-up, eight (38.1%) patients had a good clinical outcome. At follow-up, the trial of ORG 10172 in acute stroke treatment (TOAST) classification was large-vessel atherosclerosis in 13 patients (61.9%), cardioembolic in seven patients (33.3%), and undetermined in one patient (4.8%). In our series, application of the Solitaire AB stent retriever in acute BAO resulted in a high recanalization rate without procedural complications, and with good clinical outcome. Further prospective trials are needed to confirm the potential clinical benefit of this treatment approach. PMID:27312281

  14. Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

    PubMed Central

    Assenzio, Barbara; Martin, Erica L.; Stankevicius, Edgaras; Civiletti, Federica; Fontanella, Marco; Boccaletti, Riccardo; Berardino, Maurizio; Mazzeo, AnnaTeresa; Ducati, Alessandro; Simonsen, Ulf; Mascia, Luciana

    2015-01-01

    Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. Conclusions Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients

  15. Basilar Occlusion Syndromes

    PubMed Central

    Broderick, Joseph P.

    2015-01-01

    Basilar artery occlusions (BAOs) are a subset of posterior circulation strokes. Particular issues relevant to BAOs include variable and stuttering symptoms at onset resulting in delays in diagnosis, high morbidity and mortality, and uncertain best management. Despite better imaging techniques, diagnosis, and therefore treatment, is often delayed. We will present the most common signs and symptoms of posterior circulation strokes. Data on optimal treatment strategies are gathered from multiple case series, registries, and one randomized trial, which was stopped early. Possible etiologies of BAOs, acute, and subacute treatment strategies and special topics in neuroimaging of the posterior fossa are discussed. This review may be helpful to neurohospitalists who are managing patients with acute stroke as well as emergency room physicians and neurologists. PMID:26288672

  16. Unilateral cerebellar and brain stem hypoplasia in a child with a postnatal diagnosis of dissecting aneurysm in basilar artery.

    PubMed

    Akkas-Yazici, Sinem; Benbir, Gulcin; Kocer, Naci; Yalcinkaya, Cengiz

    2014-12-01

    Cerebellum is highly vulnerable in the prenatal period. Increasing experience with fetal imaging studies has demonstrated that unilateral cerebellar hypoplasia (UCH) is mainly prenatally acquired, representing disruption rather than a true malformation. Here, we report the case of a 17-month-old boy presented with a sudden onset of abnormal eye movements, who was diagnosed during routine fetal screening with UCH and brain stem hypoplasia and suffered from cerebral palsy; however, no posterior arterial system pathology was detected on cranial magnetic resonance images at that time. Following this acute event, diagnostic neuroradiological interventions revealed a dissecting aneurysm with a saccular component in midbasilar arterial segment and hypoplastic left posterior cerebral artery, which may support the ischemic disruptive mechanism in the development of prenatally detected UCH in this child. The pathogenetic mechanisms for cerebellar disruption are certainly multifactorial in origin, although ischemic arterial etiologies were often undervalued.

  17. A case of basilar artery aneurysm rupture from 1836: lessons in clinical observation and the natural history of the disease.

    PubMed

    Demetriades, Andreas K; Horiguchi, Takashi; Goodrich, James T; Kawase, Takeshi

    2014-11-01

    Although credit is given to Sir William Gull for highlighting the clinical picture of subarachnoid hemorrhage in 1859, we discuss a case presented by Mr. Egerton A. Jennings, Fellow of the Linnaean Society, published 23 years earlier in the 1836 edition of the Transactions of the Provincial Medical and Surgical Association. This case, probably the first reported in the English language of a basilar aneurysm rupture, is of medico-historical interest. Jennings provided a remarkably accurate and detailed description of the patient, who experienced coma as a result of the severity of subarachnoid hemorrhage. The detailed clinical observations on initial assessment and the description of the patient's deterioration to the time of death are a succinct representation of the natural history of this disease. The author's discussion provides evidence of a philosophy committed to medical education and progress at the time based on principles of rational observation, meticulous clinical acumen, insight into experimental physiology, and the awareness of ethical boundaries. In provincial 1836 England, similar to most of Europe, cerebral localization was elementary. Nonetheless, this case report highlights the attempt at linking structure to function by means of observation on the effects of lesioning. It provides evidence of an established thought process already in progress in England in the 19th century. It is characteristic that this thought process came from a surgical practitioner. The cultivation of practical observation in British surgical culture would allow the late 19th century surgeon scientists to match the contributions of British neurologists with landmark steps in the development and establishment of neurosurgery.

  18. Functional Independence following Endovascular Treatment for Basilar Artery Occlusion despite Extensive Bilateral Pontine Infarcts on Diffusion-Weighted Imaging: Refuting a Self-Fulfilling Prophecy

    PubMed Central

    Haussen, Diogo C.; Oliveira, Renato A.C.; Patel, Vikas; Nogueira, Raul G.

    2016-01-01

    Background and Purpose Extensive brainstem diffusion-weighted imaging (DWI) hyperintensity has been associated with poor outcomes. We aim at documenting a series of patients with extensive DWI pontine lesions who achieved independence following endovascular therapy and aggressive medical therapy in the setting of posterior circulation basilar artery occlusion (BAO). Methods This is a retrospective endovascular database review of a single-operator experience over a 9-year period for patients with (1) complete BAO, (2) extensive bilateral pontine DWI changes and (3) 90-day modified Rankin scale 0–2. Results Three out of a total of 40 patients met the inclusion criteria. Case 1 was an 18-year-old male with National Institutes of Health Stroke Scale (NIHSS) 32 on admission, treated 25 h after symptom onset. Case 2 was a 56-year-old male with NIHSS 19, treated 10 h after onset. Case 3 was a 73-year-old male with NIHSS 29, treated 6 h after onset. Full endovascular reperfusion was achieved in all 3 patients. A literature review identified 9 additional cases of extensive pontine DWI changes and good outcome. These patients were young (32 ± 22 years), mostly males (69%), presented with a relatively low posterior circulation Acute Stroke Prognosis Early CT Score (6 ± 1), were treated relatively late from last known normal (13 ± 10 h) and were mostly (84%) treated with endovascular intervention. Conclusion Extensive bilateral pontine DWI lesions among patients with BAO are not an unequivocal indicator of poor prognosis. We advise strong caution when considering these findings in the treatment decision algorithm. PMID:27781047

  19. Vasorelaxing effects of estetrol in rat arteries.

    PubMed

    Hilgers, Rob H P; Oparil, Suzanne; Wouters, Wout; Coelingh Bennink, Herjan J T

    2012-10-01

    This study compared ex vivo relaxing responses to the naturally occurring human hormone estetrol (E(4)) vs 17β-estradiol (E(2)) in eight different vascular beds. Arteries were mounted in a myograph, contracted with either phenylephrine or serotonin, and cumulative concentration-response curves (CRCs) to E(4) and E(2) (0·1-100  μmol/l) were constructed. In all arteries tested, E(4) had lower potency than E(2), although the differential effect was less in larger than smaller arteries. In uterine arteries, the nonselective estrogen receptor (ER) blocker ICI 182 780 (1  μmol/l) caused a significant rightward shift in the CRC to both E(4) and E(2), indicating that the relaxation responses were ER dependent. Pharmacological blockade of nitric oxide (NO) synthases by N(ω)-nitro-L-arginine methyl ester (L-NAME) blunted E(2)-mediated but not E(4)-mediated relaxing responses, while inhibition of prostaglandins and endothelium-dependent hyperpolarization did not alter relaxation to either E(4) or E(2) in uterine arteries. Combined blockade of NO release and action with L-NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ resulted in greater inhibition of the relaxation response to E(4) compared with E(2) in uterine arteries. Endothelium denudation inhibited responses to both E(4) and E(2), while E(4) and E(2) concentration-dependently blocked smooth muscle cell Ca(2)(+) entry in K(+)-depolarized and Ca(2)(+)-depleted uterine arteries. In conclusion, E(4) relaxes precontracted rat arteries in an artery-specific fashion. In uterine arteries, E(4)-induced relaxations are partially mediated via an endothelium-dependent mechanism involving ERs, sGC, and inhibition of smooth muscle cell Ca(2)(+) entry, but not NO synthases or endothelium-dependent hyperpolarization.

  20. Vasorelaxing effects of estetrol in rat arteries.

    PubMed

    Hilgers, Rob H P; Oparil, Suzanne; Wouters, Wout; Coelingh Bennink, Herjan J T

    2012-10-01

    This study compared ex vivo relaxing responses to the naturally occurring human hormone estetrol (E(4)) vs 17β-estradiol (E(2)) in eight different vascular beds. Arteries were mounted in a myograph, contracted with either phenylephrine or serotonin, and cumulative concentration-response curves (CRCs) to E(4) and E(2) (0·1-100  μmol/l) were constructed. In all arteries tested, E(4) had lower potency than E(2), although the differential effect was less in larger than smaller arteries. In uterine arteries, the nonselective estrogen receptor (ER) blocker ICI 182 780 (1  μmol/l) caused a significant rightward shift in the CRC to both E(4) and E(2), indicating that the relaxation responses were ER dependent. Pharmacological blockade of nitric oxide (NO) synthases by N(ω)-nitro-L-arginine methyl ester (L-NAME) blunted E(2)-mediated but not E(4)-mediated relaxing responses, while inhibition of prostaglandins and endothelium-dependent hyperpolarization did not alter relaxation to either E(4) or E(2) in uterine arteries. Combined blockade of NO release and action with L-NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ resulted in greater inhibition of the relaxation response to E(4) compared with E(2) in uterine arteries. Endothelium denudation inhibited responses to both E(4) and E(2), while E(4) and E(2) concentration-dependently blocked smooth muscle cell Ca(2)(+) entry in K(+)-depolarized and Ca(2)(+)-depleted uterine arteries. In conclusion, E(4) relaxes precontracted rat arteries in an artery-specific fashion. In uterine arteries, E(4)-induced relaxations are partially mediated via an endothelium-dependent mechanism involving ERs, sGC, and inhibition of smooth muscle cell Ca(2)(+) entry, but not NO synthases or endothelium-dependent hyperpolarization. PMID:22798015

  1. Geometrical characteristics after Y-stenting of the basilar bifurcation

    PubMed Central

    Sağlam, Muzaffer; Kızılkılıç, Osman; Anagnostakou, Vania; Yıldız, Bülent; Koçer, Naci; Işlak, Civan

    2015-01-01

    PURPOSE We aimed to investigate the angular changes after Y-stenting of the basilar bifurcation aneurysms. METHODS A total of 19 patients (age range, 27–80 years; mean age, 52.5 years) underwent Y-stent coiling for basilar bifurcation aneurysm. Three vascular angles (α, β1, β2) were measured in the anteroposterior plane. β1 and β2 represented the angles between the basilar artery and the proximal P1 segments of the right and left posterior cerebral arteries, respectively. α represented the complementary angle between the β1 and β2 angles. Angles were measured before and after stent deployment. Diameters of the basilar artery and P2 segment of the posterior cerebral artery were measured at both sides. Correlation between vascular diameter and angular change of the basilar bifurcation was investigated. RESULTS Statistically significant α, β1, and β2 angle changes were found after stent deployment (P < 0.001). There was no statistically significant relationship between the diameter of the basilar artery and the α, β1, β2 angle changes (P > 0.05). There was no statistically significant relationship between the diameter of the posterior cerebral artery and the β angle change (P > 0.05). We found a statistically significant inverse correlation between pre-stent β angle and post-stent angle change (right side, P = 0.008; left side, P < 0.001). CONCLUSION Y-stenting narrows the effective neck and straightens the vascular bifurcation angle. Most of the angular remodeling occurs on the side that had a more acute angle before stent deployment. PMID:26359879

  2. Catheterization of the Hepatic Artery Via the Left Common Carotid Artery in Rats

    SciTech Connect

    Li Xiao; Wang Yixiang, J.; Zhou Xiangping Guan Yongsong; Tang Chengwei

    2006-12-15

    The commonly used approach for rat hepatic artery catheterization is via the gastroduodenal artery, which is ligated after the procedure. A new method of rat hepatic artery catheterization via the left common carotid artery (LCCA) is described. The LCCA is repaired after catheterization. The catheterization procedures included the following: (1) opening the rat's abdominal cavity and exposing the portion of abdominal aorta at the level of the celiac trunk; (2) separating and exposing the LCCA; inserting a microguidewire and microcatheter set into the LCCA via an incision; after placement into the descending aorta, the microguidewire and microcatheter are maneuvered into the hepatic artery under direct vision; (3) after transcatheter therapy, the catheter is withdrawn and the incision at the LCCA is repaired. This technique was employed on 60 male Sprague-Dawley rats with diethylnitrosamine-induced liver cancer, using a 3F microguidewire and microcatheter set. Selective hepatic artery catheterization was successfully performed in 57 rats. One rat died during the operation and five rats died within 7 days after the procedure. It is envisaged that as experience increases, the catheterization success rate will increase and the death rate will decrease. A new approach for selective hepatic artery catheterization via the LCCA in rats is introduced, which makes repeat catheterization of this artery possible and allows large embolization particles to be delivered by using a 3F catheter.

  3. Rat Carotid Artery Balloon Injury Model

    PubMed Central

    Tulis, David Anthony

    2010-01-01

    i. Summary Numerous and diverse experimental animal models have been used over the years to examine reactions to various forms of blood vessel disease and/or injury across species and in multiple vascular beds in a cumulative effort to relate these findings to the human condition. In this context, the rat carotid artery balloon injury model is highly characterized and commonly used for investigating gross morphological, cellular, biochemical, and molecular components of the response to experimentally-induced arterial injury. The mechanical damage caused by the balloon catheter completely removes the intimal endothelial lining and creates a distending mural injury in the operated vessel. This elicits a reproducible remodeling response characterized by vascular smooth muscle cell (SMC) mitogenesis and migration (via phenotypic switching), SMC apoptosis, partial vascular endothelial cell regeneration, enhanced matrix synthesis, and establishment of an invasive neointima in time-dependent fashion. This multi-factorial process allows for investigation of these many important pathophysiological processes and can serve as a valuable “proof-of-concept” tool to verify and substantiate in vitro results; however, inherent anatomical and adaptive constraints of this in vivo model ration comparison to the diseased human system (see Note 1). In this chapter, brief overview of the materials needed and the methodologies commonly employed for successful routine performance of this important experimental animal model will be provided. Individual sub-sections will cover animal care and handling, pre- and post-operative procedures, and the surgery proper. Protocols for histopathology and morphometry and procedures for data management and interpretation pertinent to the rat carotid artery balloon injury model will be discussed in Chapter __ of this series. Notes will conclude with important caveats, limitations, and considerations for practical use of this technique. PMID:18287662

  4. Basilar vascular system supplied by only right proatlantal intersegmentary artery type 1 with aneurysm and left internal carotid occlusion: a case report and review from the literature.

    PubMed

    Ferrone, Alessandro; Brogna, Barbara; Giliberti, Raffaele; Vassallo, Pasquale; De Magistris, Giuseppe

    2016-09-01

    Persistence of proatlantal artery (PA) is a rare condition. More than 40 cases were described in the literature. Aneurysm may involve the PA itself in approximately 2% of cases, most arising from the internal carotid artery (ICA) side of PA. This case was particular because the PA showed a saccular aneurysm on the posterior wall, probably due to atherosclerosis disease and other alterations: plaque ulcerative of ICA, occlusion of left ICA, and aberrant right VA. PMID:27594943

  5. [Basilar ectasia and stroke: clinical aspects of 21 cases].

    PubMed

    de Oliveira, R de M; Cardeal, J O; Lima, J G

    1997-09-01

    Ectasia of the basilar artery (EB) occurs when its diameter is greater than normal along all or part of its course, and/or when it is abnormally tortuous. EB may cause cranial nerve dysfunction, ischemic stroke or subarachnoid hemorrhage, pseudotumor or hydrocephalus. We tried to describe cases of stroke associated with EB, analyze its frequency, clinical aspects, and the mechanisms involved in different forms of its presentation. We found 21 patients with stroke and EB. The association between EB and stroke was more prevalent in males over the age of fifty. Main symptoms were hemiparesia, cranial nerves dysfunction, and cerebellar ataxia. Cerebral infarcts associated with EB were due to different mechanisms: arterial thrombosis, artery-to-artery embolism, mass effect with angulation and obstruction of the vertebral and basilar branches. PMID:9629405

  6. Hemodynamic analysis of arterial pressure oscillations in conscious rats.

    PubMed

    Julien, C; Zhang, Z Q; Cerutti, C; Barrès, C

    1995-01-01

    This study examined the contribution of rhythmic fluctuations of regional blood flow and vascular conductance to the genesis of low- (LF, 0.27-0.74 Hz) and high- (HF, 0.76-5 Hz) frequency oscillations of arterial pressure. In conscious 15-week-old male intact (n = 11), guanethidine-sympathectomized (n = 8) and chronically sinoaortic denervated (n = 7) rats, arterial pressure and regional blood flow velocities (pulsed Doppler probes) were simultaneously recorded. Indices of subdiaphragmatic aortic, hindquarters and superior mesenteric conductances were calculated on a beat-to-beat basis over a 60-min period. Spectral power was calculated in the LF and HF bands using a fast Fourier transform algorithm. Transfer function analysis was also performed to calculate coherence and phase between arterial pressure and regional flows and conductances. In the LF band, spectral power of arterial pressure was decreased by approx. 85% in sympathectomized and approx. 54% in sinoaortic denervated rats. In the HF band, spectral power did not differ between the groups. In the three groups of rats, relations between arterial pressure and blood flow were characterized by a significant coherence in the HF band with little or no phase delay (synchronous oscillations). Relations between arterial pressure and vascular conductance were characterized in intact rats by a significant coherence in the LF band and a phase delay tending to pi radians (opposite oscillations), whereas in both sympathectomized and sinoaortic denervated rats, coherence did not reach significance. It is concluded that LF oscillations of arterial pressure are mostly secondary to rhythmic fluctuations in the vasomotor sympathetic tone in several regional circulations. Part of these oscillations originate from the synchronizing influence of the baroreceptor reflex. The study also suggests that the respiratory (HF) oscillations of arterial pressure involve fluctuations in cardiac output of purely mechanical origin. PMID

  7. Concurrent Middle Cerebral Artery Occlusion and Intra-arterial Drug Infusion via Ipsilateral Common Carotid Artery Catheter in the Rat

    PubMed Central

    Van Winkle, Jessica A.; Chen, Bo; Lei, I-Farn; Pereira, Benedict; Rajput, Padmesh S.; Lyden, Patrick D.

    2012-01-01

    Pre-clinical development of therapy for acute ischemic stroke requires robust animal models; the rodent middle cerebral artery occlusion (MCAo) model using a nylon filament inserted into the internal carotid artery is the most popular. Drug screening requires targeted delivery of test substance in a controlled manner. To address these needs, we developed a novel method for delivering substances directly into the ischemic brain during MCAo in the awake rat. An indwelling catheter is placed in the common carotid artery ipsilateral to the occlusion at the time of the surgical placement of the occluding filament. The internal and common carotid arteries are left patent to allow superfusion anterograde. The surgeries can be completed quickly to allow rapid recovery from anesthesia; tests substances can be infused at any given time for any given duration. To simulate clinical scenarios, the occluding filament can be removed minutes or hours later (reperfusion) followed by therapeutic infusions. By delivering drug intra-arterially to the target tissue, “first pass” loss in the liver is reduced and drug effects are concentrated in the ischemic zone. To validate our method, rats were infused with Evans blue dye either intra-arterially or intravenously during a 4 hour MCAo. After a 30 minute reperfusion period, the dye was extracted from each hemisphere and quantitated with a spectrophotometer. Significantly more dye was measured in the ischemic hemispheres that received the dye intra-arterially. PMID:23261656

  8. Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension.

    PubMed

    Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L

    2016-08-01

    Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension. PMID:27590754

  9. Morphological characteristics of renal artery and kidney in rats.

    PubMed

    Yoldas, Atilla; Dayan, Mustafa Orhun

    2014-01-01

    The gross anatomy and morphometry of the kidney and renal arteries were studied in the strains of laboratory rat: Sprague-Dawley (Sp) and Wistar (W) rats. Total of 106 three-dimensional endocasts of the intrarenal arteries of kidney that were prepared using standard injection-corrosion techniques were examined. A single renal artery was observed in 100% of the cases. The renal arteries were divided into a dorsal and a ventral branch. The dorsal and ventral branches were divided into two branches, the cranial and caudal branch. Renal arteries were classified into types I and II, depending on the cranial and caudal branches and their made of branching. The present study also showed that the right kidney was slightly heavier than the left one and that the kidney of the male was generally larger than that of the female. The mean live weights of the Sprague-Dawley and Wistar rats were found to be 258.26 ± 5.9 and 182.4 ± 19.05 g, respectively. The kidney weights were significantly correlated (P < 0.01) with body weights. The kidney weights were not found significantly correlated (P > 0.01) with the length of renal arteries.

  10. Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats.

    PubMed

    Hye Khan, Md Abdul; Sharma, Amit; Rarick, Kevin R; Roman, Richard J; Harder, David R; Imig, John D

    2015-01-01

    Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN). The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat.

  11. The effect of morphine in rat small mesenteric arteries.

    PubMed

    Ozdem, Sadi S; Batu, Ozlem; Tayfun, Fatma; Yalcin, Ozlem; Meiselman, Herbert J; Baskurt, Oguz K

    2005-06-01

    We investigated the effect of morphine in phenylephrine (PE)- or KCl-precontracted rat small mesenteric arteries. Morphine (10(-6)-10(-4) M) administration caused concentration-dependent relaxation responses in small mesenteric arteries precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. The relaxant responses to morphine were partially inhibited by pre-treatment of tissues with naloxone (NAL, 10(-5) M) for 20 min. The inhibitory effect of NAL on relaxant responses to morphine in PE- or KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of endothelium-intact or endothelium-denuded arterial segments with NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or cyclooxygenase (COX) inhibitor indomethacin (10(-5) M) or histamine H(1)-receptor blocker diphenhydramine (10(-6) M), for 20 min did not inhibit the relaxation responses to morphine. Small mesenteric arterial segment contractions induced by stepwise addition of calcium to high KCl solution with no calcium were almost completely inhibited by morphine. These findings suggested that morphine-induced relaxation responses in isolated rat small mesenteric arteries were neither dependent on endothelium nor blocked by NOS or COX inhibition but they rather seem to depend on an interaction of morphine with calcium influx pathways. PMID:15939674

  12. Decreased femoral arterial flow during simulated microgravity in the rat

    NASA Technical Reports Server (NTRS)

    Roer, Robert D.; Dillaman, Richard M.

    1994-01-01

    To determine whether the blood supply to the hindlimbs of rats is altered by the tail-suspension model of weightlessness, rats were chronically instrumented for the measurement of femoral artery flow. Ultrasonic transit-time flow probes were implanted into 8-wk-old Wistar-Furth rats under ketamine-xylazine anesthesia, and, after 24 h of recovery, flow was measured in the normal ambulatory posture. Next, rats were suspended and flow was measured immediately and then daily over the next 4-7 days. Rats were subsequently returned to normal posture, and flow was monitored daily for 1-3 days. Mean arterial flow decreased immediately on the rats being suspensed and continued to decrease until a new steady state of approximately 60% of control values was attained at 5 days. On the rats returning to normal posture, flow increased to levels observed before suspension. Quantile-quantile plots of blood flow data revealed a decrease in flow during both systole and diastole. The observed decrease in hindlimb blood flow during suspension suggests a possible role in the etiology of muscular atrophy and bone loss in microgravity.

  13. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  14. [Arterial and venous microanastomoses in the rat].

    PubMed

    Gianaroli, L; Bufferli, M; Livani, M F

    1980-11-15

    Arterial and venous microvascular surgery for diameters smaller than 2 mm are shown with particular care. Some technical devices are put in evidence. Besides their statistical data the Authors present immediate and long term post-operative controls which are usually applied. The most frequent causes of failure are discussed. PMID:7213480

  15. Vascular balloon injury and intraluminal administration in rat carotid artery.

    PubMed

    Zhang, Wei; Trebak, Mohamed

    2014-01-01

    The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and cellular mechanisms involved in vascular smooth muscle dedifferentiation, neointima formation and vascular remodeling. Male Sprague-Dawley rats are the most frequently employed animals for this model. Female rats are not preferred as female hormones are protective against vascular diseases and thus introduce a variation into this procedure. The left carotid is typically injured with the right carotid serving as a negative control. Left carotid injury is caused by the inflated balloon that denudes the endothelium and distends the vessel wall. Following injury, potential therapeutic strategies such as the use of pharmacological compounds and either gene or shRNA transfer can be evaluated. Typically for gene or shRNA transfer, the injured section of the vessel lumen is locally transduced for 30 min with viral particles encoding either a protein or shRNA for delivery and expression in the injured vessel wall. Neointimal thickening representing proliferative vascular smooth muscle cells usually peaks at 2 weeks after injury. Vessels are mostly harvested at this time point for cellular and molecular analysis of cell signaling pathways as well as gene and protein expression. Vessels can also be harvested at earlier time points to determine the onset of expression and/or activation of a specific protein or pathway, depending on the experimental aims intended. Vessels can be characterized and evaluated using histological staining, immunohistochemistry, protein/mRNA assays, and activity assays. The intact right carotid artery from the same animal is an ideal internal control. Injury-induced changes in molecular and cellular parameters can be evaluated by comparing the injured artery to the internal right control artery. Likewise, therapeutic modalities can be evaluated by comparing the injured and treated artery to the

  16. Basilar membrane nonlinearity and loudness.

    PubMed

    Schlauch, R S; DiGiovanni, J J; Ries, D T

    1998-04-01

    Loudness matching functions for tones for persons with one shifted-threshold ear (hearing loss and noise-shifted thresholds) and one ear within normal limits were used to derive the presumed basilar membrane (BM) input-output (I/O) function in a normal ear. The comparison was made by assuming that the BM I/O function for the ear with the cochlear threshold shift has a slope of one (a linearized cochlea). The function for the normal ear was derived from the loudness matching function based on this assumption. Comparisons were made for archival basilar membrane data [M. A. Ruggero, N. C. Rich, A. Recio, S. S. Narayan, and L. Robles, J. Acoust. Soc. Am. 101, 2151-2163 (1997)] for chinchilla and archival loudness matches for long-duration tones for persons with various degrees of cochlear hearing loss [F. Miskolczy-Fodor, J. Acoust Soc. Am. 32, 486-492 (1960)]. Comparisons were made also between BM I/O functions and ones derived from loudness matches for persons with unilateral hearing loss simulated by broadband noise. The results show a close resemblance between the basilar membrane I/O function and the function derived from loudness matches for long-duration tones, even though the comparison was between human and chinchilla data. As the degree of threshold shift increases from 40 to 80 dB, the derived BM I/O functions become shallower, with slopes for losses of 60 dB or more falling in the range of values reported for physiological data. Additional measures with short-duration tones in noise show that the slope of the loudness function and the slope of the derived basilar membrane I/O function are associated with the behavioral threshold for the tone. The results for long-duration tones suggest a correspondence between BM displacement and loudness perception in cases of recruitment, but the relation between the degree of loss and the amount of BM compression and the relation between signal duration and compression suggests that other factors, such as the neural

  17. Magnesium sulfate reverses experimental delayed cerebral vasospasm after subarachnoid hemorrhage in rats.

    PubMed

    Ram, Z; Sadeh, M; Shacked, I; Sahar, A; Hadani, M

    1991-07-01

    We induced experimental delayed cerebral vasospasm by the intracisternal injection of greater than 0.5 ml blood in 30 rats. Seventy-two hours later the basilar artery was exposed via the transclival approach and photographed at high-power magnification through an operating microscope. We then evaluated the effect of topical (n = 30) and intravenous (n = 20) magnesium sulfate on the spastic artery by computerized image analysis. A greater than 50% reduction in baseline diameter of the basilar artery was observed in the rats subjected to subarachnoid hemorrhage compared with the 10 controls (p less than 0.0001). Intravenous magnesium sulfate dilated the spastic artery to approximately 75% of the baseline diameter in control rats (p less than 0.0001). Topical magnesium sulfate caused dramatic dilation of the basilar artery in both the control and the subarachnoid hemorrhage groups to near 150% of the baseline diameter in the controls (p less than 0.001). All rats receiving intravenous magnesium sulfate reached therapeutic plasma levels of the ion. Hemodynamic effects were mild and immediately reversible upon cessation of magnesium sulfate administration. We suggest that magnesium has a role in the treatment of subarachnoid hemorrhage-induced vasospasm in humans.

  18. Post-Treatment Hemodynamics of a Basilar Aneurysm and Bifurcation

    PubMed Central

    Ortega, J.; Hartman, J.; Rodriguez, J.; Maitland, D.

    2009-01-01

    To investigate whether or not a successful aneurysm treatment procedure can subject a parent artery to harmful hemodynamic stresses, computational fluid dynamics simulations are performed on a patient-specific basilar aneurysm and bifurcation before and after a virtual endovascular treatment. Prior to treatment, the aneurysm at systole is filled with a periodic train of vortex tubes, which form at the aneurysm neck and advect upwards into the dome. Following the treatment procedure however, the motion of the vortex train is inhibited by the aneurysm filling material, which confines the vortex tubes to the region beneath the aneurysm neck. Analysis of the post-treatment flow field indicates that the impingement of the basilar artery flow upon the treated aneurysm neck and the close proximity of a vortex tube to the parent artery wall increase the maximum wall shear stresses to values approximately equal to 50 Pa at systole. Calculation of the time-averaged wall shear stresses indicates that there is a 1.4 × 9 10−7 m2 area on the parent artery exposed to wall shear stresses greater than 37.9 Pa, a value shown by Fry [Circ. Res. 22(2):165–197, 1968] to cause severe damage to the endothelial cells that line the artery wall. The results of this study demonstrate that it is possible for a treatment procedure, which successfully isolates the aneurysm from the circulation and leaves no aneurysm neck remnant, to elevate the hemodynamic stresses to levels that are injurious to the artery wall. PMID:18629647

  19. Intraaneurysmal embolization of an unruptured basilar tip aneurysm associated with moyamoya disease.

    PubMed

    Kagawa, K; Ezura, M; Shirane, R; Takahashi, A; Yoshimoto, T

    2001-09-01

    We describe a patient with moyamoya disease associated with an unruptured basilar tip aneurysm which was treated by endovascular embolization using Guglielmi detachable coils (GDCs). A 53-year-old man presented with left hemiparesis persisting for 3 mon ths before admission. Cerebral angiography revealed occlusion of the bilateral middle cerebral arteries and the left anterior cerebral artery, stenosis of the right anterior cerebral artery, and basal moyamoya vessels. In addition, a saccular small aneurysm was seen at the top of the basilar artery. The aneurysm was completely embolized by intraaneurysmal GDCs. Direct surgical clipping is often selected for the treatment of posterior fossa aneurysms in moyamoya disease. However, complete clipping is usually difficult due to the difficulties in operative technique associated with moyamoya disease. We suggest that the endovascular treatment using GDCs is comparatively safe and effective for the treatment of surgically difficult aneurysms in patients with moyamoya disease.

  20. Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat.

    PubMed

    Arbab, M A; Wiklund, L; Svendgaard, N A

    1986-11-01

    Peripheral sources of cerebral vascular innervation have been investigated with retrograde and anterograde neuronal tracing of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) in the rat. For retrograde identification of sources of innervation, WGA-HRP was applied to the exposed basilar artery through a fine slit in the overlying meninges, and sections of brain and peripheral ganglia were reacted with tetramethylbenzidine for detection of the tracer. A high density of tetramethylbenzidine reaction product was observed around the basilar artery and in the surrounding pial tissue, but the application sites were not completely selective since some tracer always had spread into the ventral brain stem. Retrogradely labelled cell bodies were identified in the superior cervical, stellate, first and second spinal, and trigeminal ganglia, i.e. these ganglia may represent origins of basilar artery innervation. In a second series of experiments, microinjections of WGA-HRP were placed into the indicated ganglia to obtain anterograde labelling of nerve fibres on whole-mounts of the cerebral vessels. Injections into trigeminal ganglia labelled nerve fibres on the ipsilateral half of the circle of Willis, as well as the contralateral anterior cerebral artery and the rostral part of the basilar artery. The first and second spinal ganglia projected to the vertebrobasilar arteries, while the ipsilateral part of the internal carotid (outside the circle of Willis) received fibres from the second spinal ganglion. Nerve fibres originating in trigeminal and spinal ganglia were organised in bundles, and between these a sparse plexus of thin single fibres appeared. Injection of WGA-HRP into superior cervical ganglion labelled a plexus of nerve fibres on the ipsilateral circle of Willis and the (rostral) basilar artery. These experiments demonstrated the origin and distribution of sympathetic and sensory innervation to major cerebral arteries in the rat.

  1. Management of basilar invagination: A historical perspective

    PubMed Central

    Shah, Abhidha; Serchi, Elena

    2016-01-01

    For a long time the terms basilar invagination and platybasia were used interchangeably. Basilar invagination has been defined as a prolapse of the vertebral column into the spinal cord. Platybasia is defined as an abnormal obtuse angle between the anterior skull base and the clivus. The authors review the existing literature and summarize the historical and modern perspectives in the management of basilar invagination. From radiological curiosities, the subject of basilar invagination is now viewed as eminently treatable. The more pronounced understanding of the subject has taken place in the last three decades when on the basis of understanding of the biomechanical subtleties the treatment paradigm has remarkably altered. From surgery that involved decompression of the region, stabilization and realignment now form the basis of treatment.

  2. Middle cerebral artery alterations in a rat chronic hypoperfusion model

    PubMed Central

    Márquez-Martín, Ana; Jiménez-Altayó, Francesc; Dantas, Ana P.; Caracuel, Laura; Planas, Anna M.

    2012-01-01

    Chronic cerebral hypoperfusion (CHP) induces microvascular changes that could contribute to the progression of vascular cognitive impairment and dementia in the aging brain. This study aimed to analyze the effects of CHP on structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) after bilateral common carotid artery occlusion (BCCAO) in adult male Wistar rats. Sham animals underwent a similar surgical procedure without carotid artery (CA) ligation. After 15 days of occlusion, MCA and CA were dissected and MCA structural, mechanical, and myogenic properties were assessed by pressure myography. Collagen I/III expression was determined by immunofluorescence in MCA and CA and by Western blot in CA. mRNA levels for 1A1, 1A2, and 3A1 collagen subunits were quantified by quantitative real-time PCR in CA. Matrix metalloproteinase (MMP-1, MMP-2, MMP-9, and MMP-13) and hypoxia-inducible factor-1α (HIF-1α) protein expression were determined in CA by Western blot. BCCAO diminished cross-sectional area, wall thickness, and wall-to-lumen ratio. Nevertheless, whereas wall stress was increased, stiffness was not modified and myogenic response was diminished. Hypoperfusion triggered HIF-1α expression. Collagen I/III protein expression diminished in MCA and CA after BCCAO, despite increased mRNA levels for 1A1 and 3A1 collagen subunits. Therefore, the reduced collagen expression might be due to proteolytic degradation, since the expression of MMP-1 and MMP-9 increased in the CA. These data suggest that BCCAO induces hypotrophic remodeling by a mechanism that involves a reduction of collagen I/III in association with increased MMP-1 and MMP-9 and that decreases myogenic tone in major arteries supplying the brain. PMID:22096118

  3. [Mechanism of losartan suppressing vascular calcification in rat aortic artery].

    PubMed

    Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

    2016-08-01

    Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID:27412937

  4. H2S induces vasoconstriction of rat cerebral arteries via cAMP/adenylyl cyclase pathway.

    PubMed

    Li, Sen; Ping, Na-Na; Cao, Lei; Mi, Yan-Ni; Cao, Yong-Xiao

    2015-12-15

    Hydrogen sulfide (H2S), traditionally known for its toxic effects, is now involved in regulating vascular tone. Here we investigated the vasoconstrictive effect of H2S on cerebral artery and the underlying mechanism. Sodium hydrosulfide (NaHS), a donor of H2S, concentration-dependently induced vasoconstriction on basilar artery, which was enhanced in the presence of isoprenaline, a β-adrenoceptor agonist or forskolin, an adenylyl cyclase activator. Administration of NaHS attenuated the vasorelaxant effects of isoprenaline or forskolin. Meanwhile, the NaHS-induced vasoconstriction was diminished in the presence of 8B-cAMP, an analog of cAMP, but was not affected by Bay K-8644, a selective L-type Ca(2+) channel agonist. These results could be explained by the revised effects of NaHS on isoprenaline-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. Additionally, NaHS-induced vasoconstriction was enhanced by removing the endothelium or in the presence of L-NAME, an inhibitor of nitric oxide synthase. L-NAME only partially attenuated the effect of NaHS which was given together with forskolin on the pre-contracted artery. In conclusion, H2S induces vasoconstriction of cerebral artery via, at least in part, cAMP/adenylyl cyclase pathway.

  5. Post-Treatment Hemodynamics of a Basilar Aneurysm and Bifurcation

    SciTech Connect

    Ortega, J; Hartman, J; Rodriguez, J; Maitland, D

    2008-01-16

    Aneurysm re-growth and rupture can sometimes unexpectedly occur following treatment procedures that were initially considered to be successful at the time of treatment and post-operative angiography. In some cases, this can be attributed to surgical clip slippage or endovascular coil compaction. However, there are other cases in which the treatment devices function properly. In these instances, the subsequent complications are due to other factors, perhaps one of which is the post-treatment hemodynamic stress. To investigate whether or not a treatment procedure can subject the parent artery to harmful hemodynamic stresses, computational fluid dynamics simulations are performed on a patient-specific basilar aneurysm and bifurcation before and after a virtual endovascular treatment. The simulations demonstrate that the treatment procedure produces a substantial increase in the wall shear stress. Analysis of the post-treatment flow field indicates that the increase in wall shear stress is due to the impingement of the basilar artery flow upon the aneurysm filling material and to the close proximity of a vortex tube to the artery wall. Calculation of the time-averaged wall shear stress shows that there is a region of the artery exposed to a level of wall shear stress that can cause severe damage to endothelial cells. The results of this study demonstrate that it is possible for a treatment procedure, which successfully excludes the aneurysm from the vascular system and leaves no aneurysm neck remnant, to elevate the hemodynamic stresses to levels that are injurious to the immediately adjacent vessel wall.

  6. Modification of sympathetic neuronal function in the rat tail artery by dietary lipid treatment

    SciTech Connect

    Panek, R.L.; Dixon, W.R.; Rutledge, C.O.

    1985-06-01

    The effect of dietary lipid treatment on sympathetic neuronal function was examined in isolated perfused tail arteries of adult rats. The hypothesis that dietary manipulations alter the lipid environment of receptor proteins which may result in the perturbation of specific membrane-associated processes that regulate peripheral adrenergic neurotransmission in the vasculature was the basis for this investigation. In the present study, rats were fed semisynthetic diets enriched in either 16% coconut oil (saturated fat) or 16% sunflower oil (unsaturated fat). The field stimulation-evoked release of endogenous norepinephrine and total /sup 3/H was decreased significantly in rats receiving the coconut oil diet when compared to either sunflower oil- or standard lab chow-fed rats. Norepinephrine content in artery segments from coconut oil-treated rats was significantly higher compared to either sunflower oil- or standard lab chow-fed rats. Tail arteries from rats receiving the coconut oil diet displayed significantly lower perfusion pressure responses to nerve stimulation at all frequencies tested when compared to the sunflower oil- or standard lab chow-fed rats. Vasoconstrictor responses of perfused tail arteries exposed to exogenous norepinephrine resulted in an EC50 for norepinephrine that was not changed by the dietary treatment, but adult rats receiving the sunflower oil diet displayed a significantly greater maximum response to exogenous norepinephrine (10(-5) M) compared to arteries from either coconut oil- or standard lab chow-fed rats.

  7. Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

    PubMed Central

    Santhanam, Anantha Vijay R.; Smith, Leslie A.; Katusic, Zvonimir S.

    2009-01-01

    Background The role of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in control of cerebral circulation is poorly understood. The present study was designed to investigate the cerebral vascular effects of BDNF in vivo. Methods Replication incompetent adenovirus encoding either rat BDNF (AdBDNF) or green fluorescent protein (AdGFP) was injected intracisternally into rabbits. Forty eight hours later, animals were euthanized. Plasma and cerebrospinal fluid (CSF) levels of BDNF were measured by ELISA, vasomotor function of isolated basilar arteries was studied in organ chambers, protein expression in the basilar arteries was studied by Western blotting, prostanoid levels measured by ELISA and cyclic adenosine 3′,5′-monophosphate (cyclic AMP) levels were measured by radioimmunoassay. Results The levels of BDNF in the CSF were significantly elevated in AdBDNF-treated rabbits as compared to AdGFP-treated rabbits (37 ± 5 ng/ml vs. 0.006 ± 0.003 ng/ml, respectively, P<0.05, n=14). Western blotting studies revealed that in basilar arteries AdBDNF increased protein expression of prostacyclin (PGI2) synthase, while expression of endothelial nitric oxide synthase (eNOS) and phosphorylated (Ser 1177) eNOS remained unchanged. During incubation with arachidonic acid (1 μmol/L), PGI2 production and levels of cyclic AMP were significantly elevated only in AdBDNF-treated rabbit basilar arteries (P<0.05, n=6). Relaxations to acetylcholine (10−9 to 10−5 mol/L) and arachidonic acid (10−9 to 10−5 mol/L) were significantly potentiated in basilar arteries from rabbits injected with AdBDNF. Potentiation of relaxations to acetylcholine in AdBDNF-treated basilar arteries was inhibited by the non-selective cyclooxygenase inhibitor, indomethacin (10−5 mol/l, P<0.05, n=6) and constitutive phospholipase A2 inhibitor, AACOCF3 (2 × 10−5 mol/L, P<0.05, n=5). Conclusion Our results demonstrate that in cerebral arteries, BDNF

  8. Modification by choline of adrenergic transmission in rat mesenteric arteries

    PubMed Central

    Malik, K. U.; McGiff, J. C.

    1971-01-01

    1. The action of choline on the vasoconstrictor responses of the perfused mesenteric arteries of the rat to sympathetic nerve stimulation and to injected noradrenaline has been investigated. 2. The infusion of choline (500 μg/ml), for periods of 15 s, increased the response to sympathetic nerve stimulation, whereas the infusion of the same concentration for 20 min greatly reduced the response to nerve stimulation. Choline (up to 500 μg/ml), infused either for short or long periods, did not alter the response to injected noradrenaline. 3. The inhibitory action of choline on the response to nerve stimulation was abolished either by an increase in the calcium concentration from 1·8 to 5·4 mM or by simultaneous infusion of (+)-amphetamine or atropine. 4. The results suggest that choline in concentrations of 500 μg/ml has the same effect on adrenergic transmission in mesenteric arteries as acetylcholine at concentrations of 5 ng/ml. PMID:4339884

  9. Inhomogeneous vasodilatory responses of rat tail arteries to heat stress: evaluation by synchrotron radiation microangiography.

    PubMed

    Kuwabara, Eriko; Furuyama, Fujiya; Ito, Kunihisa; Tanaka, Etsuro; Hattan, Naoichiro; Fujikura, Hisanori; Kimura, Koji; Goto, Takako; Hayashi, Takashi; Taira, Hiroyuki; Shinozaki, Yoshiro; Umetani, Keiji; Hyodo, Kazuyuki; Tanioka, Kenkichi; Mochizuki, Ryo; Kawai, Toshiaki; Koide, Shirosaku; Mori, Hidezo

    2002-10-01

    Tail blood flow is crucial for dissipating body heat in rats. Angiographies are convenient tools to evaluate tail circulation. However, conventional angiographies do not have sufficient sensitivity or spatial resolution for small vessels. Recently, we developed a novel microangiographic system using monochromatic synchrotron radiation and a high-definition video camera system. Here, we report an evaluation of rat tail circulation under heat stress using the synchrotron radiation microangiographic system. We performed an experiment using the microangiography of the caudal artery before and after heating up WKAH/HkmSlc rats to rectal temperature of 39 degrees C. The images were digitized and temporal subtraction was performed, and the diameters of caudal arteries were evaluated. After heating, the medial caudal artery was markedly dilated (320 +/- 53 to 853 +/- 243 micro m in diameter, p<0.001), while no significant change was observed in the lateral caudal arteries (139 +/- 42 to 167 +/- 73 micro m) and segmental anastomosing vessels. The heat stress allowed for visualization of the superficial caudal arteries with a diameter of approximately 60 micro m, not visible prior to heating. Thus, synchrotron radiation microangiography demonstrated that the rat tail possessed dual sets of arteries; one set was highly sensitive to heat-induced vasodilation (medial caudal artery and superficial caudal arteries) and the other set was less sensitive (lateral caudal arteries and segmental anastomosing vessels).

  10. Diminished contractile responses of isolated conduit arteries in two rat models of hypertension.

    PubMed

    Zemancíková, Anna; Török, Jozef

    2013-08-31

    Hypertension is accompanied by thickening of arteries, resulting in marked changes in their passive and active mechanical properties. The aim of this study was to demonstrate that the large conduit arteries from hypertensive individuals may not exhibit enhanced contractions in vitro, as is often claimed. Mechanical responses to vasoconstrictor stimuli were measured under isometric conditions using ring arterial segments isolated from spontaneously hypertensive rats, N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated Wistar rats, and untreated Wistar rats serving as normotensive control. We found that thoracic aortas from both types of hypertensive rats had a greater sensitivity but diminished maximal developed tension in response to noradrenaline, when compared with that from normotensive rats. In superior mesenteric arteries, the sensitivity to noradrenaline was similar in all examined rat groups but in L-NAME-treated rats, these arteries exhibited decreased active force when stimulated with high noradrenaline concentrations, or with 100 mM KCl. These results indicate that hypertension leads to specific biomechanical alterations in diverse arterial types which are reflected in different modifications in their contractile properties.

  11. Altered potassium ATP channel signaling in mesenteric arteries of old high salt-fed rats

    PubMed Central

    Whidden, Melissa A.; Basgut, Bilgen; Kirichenko, Nataliya; Erdos, Benedek; Tümer, Nihal

    2016-01-01

    [Purpose] Both aging and the consumption of a high salt diet are associated with clear changes in the vascular system that can lead to the development of cardiovascular disease; however the mechanisms are not clearly understood. Therefore, we examined whether aging and the consumption of excess salt alters the function of potassium ATP-dependent channel signaling in mesenteric arteries [Methods] Young (7 months) and old (29 months) Fischer 344 x Brown Norway rats were fed a control or a high salt diet (8% NaCl) for 12 days and mesenteric arteries were utilized for vascular reactivity measurements. [Results] Acetylcholine-induced endothelium relaxation was significantly reduced in old arteries (81 ± 4%) when compared with young arteries (92 ± 2%). Pretreatment with the potassium-ATP channel blocker glibenclamide reduced relaxation to acetylcholine in young arteries but did not alter dilation in old arteries. On a high salt diet, endothelium dilation to acetylcholine was significantly reduced in old salt arteries (60 ± 3%) when compared with old control arteries (81 ± 4%). Glibenclamide reduced acetylcholine-induced dilation in young salt arteries but had no effect on old salt arteries. Dilation to cromakalim, a potassium-ATP channel opener, was reduced in old salt arteries when compared with old control arteries. [Conclusion] These findings demonstrate that aging impairs endothelium-dependent relaxation in mesenteric arteries. Furthermore, a high salt diet alters the function of potassium-ATP-dependent channel signaling in old isolated mesenteric arteries and affects the mediation of relaxation stimuli. PMID:27508155

  12. Persistent trigeminal artery: in situ thrombosis and associated perforating vessel infarction.

    PubMed

    Gaughen, John R; Starke, Robert M; Durst, Christopher R; Evans, Avery J; Jensen, Mary E

    2014-06-01

    We report a patient with progressive brainstem infarction despite medical therapy. The patient was transferred to our institution for potential angioplasty of basilar stenosis. Imaging review demonstrated persistent trigeminal artery in situ thrombosis and associated perforating vessel infarction. Persistent trigeminal arteries are commonly associated with an atretic basilar artery and interventional treatment can result in significant morbidity and mortality.

  13. Hyper-reactivity of cerebral arteries from ovariectomized rats: therapeutic benefit of tamoxifen.

    PubMed

    Thorin, Eric; Pham-Dang, Mylan; Clement, Robert; Mercier, Isabelle; Calderone, Angelino

    2003-12-01

    1. An increased incidence of systemic hypertension has been documented in postmenopausal women and identified as an independent risk factor in the development of cerebrovascular stroke. The present study examined whether cerebrovascular reactivity was increased in the hypertensive ovariectomized rat, and explored the potential therapeutic benefit of the partial estrogen receptor agonist tamoxifen. 2. Female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX, n=16) or a sham operation (n=8). At 6-week postsurgery, rats were anesthetized to assess ventricular contractility and blood pressure. In a second series of experiments, OVX rats (n=8) were given tamoxifen starting 3 weeks postsurgery, and continued for 3 weeks. At the end of each protocol, the middle cerebral artery was harvested and rings were mounted in wire-myographs to measure isometric tension. 3. Systolic arterial pressure (SAP) was significantly increased (P<0.05) in the OVX rat (174+/-8 mmHg), as compared to sham (135+/-6 mmHg). The resting tension of isolated cerebral arteries from OVX rats (186+/-15 mg) was significantly elevated (P<0.05), as compared to sham (129+/-9 mg). Phenylephrine treatment did not elicit a constriction of cerebral arteries isolated from sham rats, whereas a potent response (P<0.05) was observed in OVX rats. Nitric oxide (NO) synthase inhibition with L-NNA led to a limited contraction in sham rats (8+/-3% of Emax), whereas a significant (P<0.05) increase was observed in OVX rats (34+/-12% of Emax). Lastly, vascular sensitivity (pD2) to sodium nitroprusside was significantly increased (P<0.05) in OVX rats, as compared to sham. 4. Tamoxifen therapy normalized the resting tension of isolated cerebral arteries from OVX rats, abrogated phenylephrine-mediated contraction, and modestly reduced SAP. By contrast, tamoxifen treatment of OVX rats did not attenuate L-NNA-mediated contractile response of cerebral arteries. 5. These data demonstrate that the cerebral artery

  14. Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke.

    PubMed

    Liu, S Q; Fung, Y C

    1993-09-01

    The effect of cigarette smoke on the structure and mechanical properties of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times per day with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The volume fractions of the cells, including smooth muscle cells and fibroblasts, and extracellular matrix components, including collagen, elastin, and remainder (components not specified in this study), of the pulmonary arteries of approximately 450 microns in external diameter (at zero pressure) were determined in smoke-exposed and control rats by using an electron microscopic method. It was found that the volume fractions of the fibroblasts, the collagenous bundles, and the elastic laminae of the pulmonary arteries were increased significantly, whereas those of the smooth muscle cells and the remainder were decreased significantly in both the 2- and 3-month smoke-exposed rats in comparison with those of the corresponding control rats. The mechanical properties of the pulmonary arteries were determined based on the in vitro dimensional measurement of the vessels at various inflation pressures and zero-stress state. An increase in the stiffness of the pulmonary arteries was found in both the 2- and 3-month smoke-exposed rats. We conclude that cigarette smoke can induce structural and mechanical remodeling in the pulmonary arteries of rats. PMID:8368648

  15. Spinal cord injury increases the reactivity of rat tail artery to angiotensin II

    PubMed Central

    Al Dera, Hussain; Brock, James A.

    2015-01-01

    Studies in individuals with spinal cord injury (SCI) suggest the vasculature is hyperreactive to angiotensin II (Ang II). In the present study, the effects of SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been investigated. In addition, the effects of SCI on the facilitatory action of Ang II on nerve-evoked contractions of these vessels were determined. Isometric contractions of artery segments from T11 (tail artery) or T4 (mesenteric arteries) spinal cord-transected rats and sham-operated rats were compared 6–7 weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve-evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked contractions and the facilitatory effect of Ang II on nerve-evoked contractions. By contrast, SCI did not detectably change the responses of mesenteric arteries to Ang II. These findings provide the first direct evidence that SCI increases the reactivity of arterial vessels to Ang II. In addition, in tail artery, the findings indicate that Ang II may contribute to modifying their responses following SCI. PMID:25610365

  16. Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries.

    PubMed

    Jackson-Weaver, Olan; Osmond, Jessica M; Naik, Jay S; Gonzalez Bosc, Laura V; Walker, Benjimen R; Kanagy, Nancy L

    2015-12-01

    Ca(+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and promote vasodilation by activating large-conductance Ca(2+)-activated potassium channels and inhibiting myogenic tone. We have previously reported that exposing rats to intermittent hypoxia (IH) to simulate sleep apnea augments myogenic tone in mesenteric arteries through loss of hydrogen sulfide (H2S)-induced dilation. Because we also observed that H2S can increase Ca(2+) spark activity, we hypothesized that loss of H2S after IH exposure reduces Ca(2+) spark activity and that blocking Ca(2+) spark generation reduces H2S-induced dilation. Ca(2+) spark activity was lower in VSMC of arteries from IH compared with sham-exposed rats. Furthermore, depolarizing VSMC by increasing luminal pressure (from 20 to 100 mmHg) or by elevating extracellular [K(+)] increased spark activity in VSMC of arteries from sham rats but had no effect in arteries from IH rats. Inhibiting endogenous H2S production in sham arteries prevented these increases. NaHS or phosphodiesterase inhibition increased spark activity to the same extent in sham and IH arteries. Depolarization-induced increases in Ca(2+) spark activity were due to increased sparks per site, whereas H2S increases in spark activity were due to increased spark sites per cell. Finally, inhibiting Ca(2+) spark activity with ryanodine (10 μM) enhanced myogenic tone in arteries from sham but not IH rats and blocked dilation to exogenous H2S in arteries from both sham and IH rats. Our results suggest that H2S regulates RyR activation and that H2S-induced dilation requires Ca(2+) spark activation. IH exposure decreases endogenous H2S-dependent Ca(2+) spark activation to cause membrane depolarization and enhance myogenic tone in mesenteric arteries.

  17. Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats.

    PubMed

    Pourageaud, F; Freslon, J L

    1995-01-01

    To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15-25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D100) were determined and vessels were set up to a normalized internal diameter (0.9 D100). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 microM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 microM) but not D-arginine (100 microM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 microM] in MRA; serotonin, 5-HT [10 microM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 microM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 microM) completely inhibited relaxations induced by acetylcholine (0.01-10 microM) in all types of precontracted arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Regional arterial stress-strain distributions referenced to the zero-stress state in the rat.

    PubMed

    Zhao, Jingbo; Day, Judd; Yuan, Zhuang Feng; Gregersen, Hans

    2002-02-01

    Morphometric and stress-strain properties were studied in isolated segments of the thoracic aorta, abdominal aorta, left common carotid artery, left femoral artery, and the left pulmonary artery in 16 male Wistar rats. The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. Outer wall dimensions were obtained from digitized images of the arterial segments at different pressures as well as at no-load and zero-stress states. The results showed that the morphometric data, such as inner and outer circumference, wall and lumen area, wall thickness, wall thickness-to-inner radius ratio, and normalized outer diameter, as a function of the applied pressures, differed between the five arteries (P < 0.01). The opening angle was largest in the pulmonary artery and smallest in thoracic aorta (P < 0.01). The absolute value of both the inner and outer residual strain and the residual strain gradient were largest in the femoral artery and smallest in the thoracic aorta (P < 0.01). In the circumferential and longitudinal direction, the arterial wall was stiffest in the femoral artery and in the thoracic aorta, respectively, and most compliant in the pulmonary artery. These results show that the morphometric and biomechanical properties referenced to the zero-stress state differed between the five arterial segments. PMID:11788411

  19. Structural and functional analysis of small arteries from young spontaneously hypertensive rats.

    PubMed

    Dickhout, J G; Lee, R M

    1997-03-01

    We studied structural and functional changes of small muscular arteries from the mesenteric vascular bed of young spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) using a new morphometric protocol involving the use of confocal microscopy and a pressurized artery system. At 3 and 4 weeks of age, systolic pressure of SHR and WKY was similar; however, significant structural changes in the mesenteric vasculature were already present in SHR. Arteries fixed under pressure in vitro from SHR had a larger medial volume and increased number of smooth muscle cell layers but similar lumen size compared with arteries from WKY in maximally relaxed conditions. Functional studies showed that SHR arteries contracted more in response to stimulation by KCl and norepinephrine, resulting in a significantly smaller lumen size in these vessels than in those from WKY. SHR arteries precontracted with KCl were also able to maintain a smaller lumen diameter than WKY arteries when challenged with increasing pressure levels. No difference in the sensitivity of response of these arteries to norepinephrine stimulation was found. At 3 and 4 weeks of age, mesenteric arteries from some SHR and WKY were not responsive to periarterial nerve stimulation, and the number of responders was higher in the WKY than SHR. However, a greater degree of contraction was found in SHR arteries responding to field stimulation at 4 weeks than in WKY arteries. We conclude that there is a temporal difference in the rate of functional maturation of the innervation in SHR arteries compared with WKY arteries. Structural changes of the small muscular arteries, caused by an increase in the medial volume, and increased number of smooth muscle cell layers are primary changes that contribute to the development of hypertension in the SHR because these changes are present at the age when blood pressure is similar in SHR and WKY.

  20. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH. PMID:25490411

  1. Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats.

    PubMed

    Sun, Biao; Zhang, Li-Fan; Gao, Fang; Ma, Xiao-Wu; Zhang, Miao-Li; Liu, Jian; Zhang, Le-Ning; Ma, Jin

    2004-09-01

    This study was designed to clarify whether simulated microgravity-induced differential adaptational changes in cerebral and hindlimb arteries could be prevented by daily short-period restoration of the normal distribution of transmural pressure across arterial vasculature by either dorsoventral or footward gravitational loading. Tail suspension (Sus) for 28 days was used to simulate cardiovascular deconditioning due to microgravity. Daily standing (STD) for 1, 2, or 4 h, or +45 degrees head-up tilt (HUT) for 2 or 4 h was used to provide short-period dorsoventral or footward gravitational loading as countermeasure. Functional studies showed that Sus alone induced an enhancement and depression in vasoconstrictor responsiveness of basilar and femoral arterial rings, respectively, as previously reported. These differential functional alterations can be prevented by either of the two kinds of daily gravitational loading treatments. Surprisingly, daily STD for as short as 1 h was sufficient to prevent the differential functional changes that might occur due to Sus alone. In morphological studies, the effectiveness of daily 4-h HUT or 1-h STD in preventing the differential remodeling changes in the structure of basilar and anterior tibial arteries induced by Sus alone was examined by histomorphometry. The results showed that both the hypertrophic and atrophic changes that might occur, respectively, in cerebral and hindlimb arteries due to Sus alone were prevented not only by daily HUT for 4 h but also by daily STD even for 1 h. These data indicate that daily gravitational loading by STD for as short as 1 h is sufficient to prevent differential adaptational changes in function and structure of vessels in different anatomic regions induced by a medium-term simulated microgravity.

  2. Dynamics of change in rat arterial pressure under conditions of immobilization

    NASA Technical Reports Server (NTRS)

    Yumatov, Y. A.; Skotselyas, Y. G.; Ivanona, L. I.

    1980-01-01

    Emotional stress developed in immobilized rats was shown to be accompanied by changes in the regulation of arterial pressure and the frequency of cardiac contractions. A group of adapting rats displayed definite resistance to emotional stress, while a group of rats incapable of adapting to acute emotional stress died with characteristics of cardiovascular insufficiency. The mechanisms providing resistance to emotional stress in numerous conflict situations were analyzed.

  3. 5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats.

    PubMed Central

    MacLean, M. R.; Sweeney, G.; Baird, M.; McCulloch, K. M.; Houslay, M.; Morecroft, I.

    1996-01-01

    1. We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT1 agonist), and sumatriptan (5-HT1D-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT1 + 2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HT1D receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cyclic monophosphate ([cyclic AMP]i) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]i) were determined and we assessed the degree of inherent tone in the vessels under study. 2. 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 +/- 0.1, 5.3 +/- 0.1, 5.0 +/- 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 +/- 0.2, 6.3 +/- 0.2, 6.4 +/- 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4 +/- 0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +/- 0.2; 5-CT, 5.4 +/- 0.2). 5-CT also caused a contraction in the main pulmonary artery (pEC50: 6.0 +/- 0.3). 3. Ketanserin (1 nM-1 microM) caused a competitive antagonism of the 5-HT response in all vessels tested. In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary

  4. Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow.

    PubMed

    Li, Xiaohui; Du, Junbao; Jin, Hongfang; Geng, Bin; Tang, Chaoshu

    2008-11-01

    This study aimed to explore the effect of sodium hydrosulfide (NaHS) on pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham + NaHS (an H2S donor) group, and shunt + NaHS group. After 11 weeks of shunting, mean pulmonary artery pressure (MPAP), relative median area (RMA) of pulmonary arteries, H2S concentration in lung tissues, plasma endothelin-1 (ET-1) levels, and ET-1 mRNA in lung tissues were investigated. Collagen I and collagen III were evaluated by immunohistochemistry. Hydroxyproline assay and Sirius-red staining were performed. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 11 weeks of shunting, rats showed a significant pulmonary hypertension and pulmonary artery collagen remodeling in association with a decrease in lung tissue H2S content. After NaHS treatment for 11 weeks, lung tissue H(2)S content was increased, whereas MPAP was attenuated and RMA was reduced. Meanwhile, pulmonary artery collagen I and collagen III protein expressions of intra-acinar pulmonary arteries were inhibited, but MMP-13/TIMP-1 ratio was augmented with a decreased plasma ET-1 content and lung tissue ET-1mRNA and CTGF expressions. The downregulation of H(2)S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.

  5. Oxygen sensitivity of mitochondrial function in rat arterial chemoreceptor cells.

    PubMed

    Buckler, Keith J; Turner, Philip J

    2013-07-15

    The mechanism of oxygen sensing in arterial chemoreceptors is unknown but has often been linked to mitochondrial function. A common criticism of this hypothesis is that mitochondrial function is insensitive to physiological levels of hypoxia. Here we investigate the effects of hypoxia (down to 0.5% O2) on mitochondrial function in neonatal rat type-1 cells. The oxygen sensitivity of mitochondrial [NADH] was assessed by monitoring autofluorescence and increased in hypoxia with a P50 of 15 mm Hg (1 mm Hg = 133.3 Pa) in normal Tyrode or 46 mm Hg in Ca(2+)-free Tyrode. Hypoxia also depolarised mitochondrial membrane potential (m, measured using rhodamine 123) with a P50 of 3.1, 3.3 and 2.8 mm Hg in normal Tyrode, Ca(2+)-free Tyrode and Tyrode containing the Ca(2+) channel antagonist Ni(2+), respectively. In the presence of oligomycin and low carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP; 75 nm) m is maintained by electron transport working against an artificial proton leak. Under these conditions hypoxia depolarised m/inhibited electron transport with a P50 of 5.4 mm Hg. The effects of hypoxia upon cytochrome oxidase activity were investigated using rotenone, myxothiazol, antimycin A, oligomycin, ascorbate and the electron donor tetramethyl-p-phenylenediamine. Under these conditions m is maintained by complex IV activity alone. Hypoxia inhibited cytochrome oxidase activity (depolarised m) with a P50 of 2.6 mm Hg. In contrast hypoxia had little or no effect upon NADH (P50 = 0.3 mm Hg), electron transport or cytochrome oxidase activity in sympathetic neurons. In summary, type-1 cell mitochondria display extraordinary oxygen sensitivity commensurate with a role in oxygen sensing. The reasons for this highly unusual behaviour are as yet unexplained.

  6. The effects of quinapril and atorvastatin on artery structure and function in adult spontaneously hypertensive rats.

    PubMed

    Yang, Lufang; Gao, Yu-Jing; Lee, Robert M K W

    2005-08-22

    We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions. We found that a combined treatment with quinapril and atorvastatin lowered systolic blood pressure in both adult SHR and WKY rats and decreased medial thickness and volume and the number of smooth muscle cell layers in mesenteric arteries, as well as media-to-lumen ratio in the interlobular arteries from SHR but not in those from WKY rats. The number of apoptotic smooth muscle cells was higher in the mesenteric arteries from control WKY rats than control SHR and treatment increased the number of apoptotic smooth muscle cells in the arteries from both SHR and WKY rats. Treatment with quinapril and atorvastatin reduced ventricular weight in SHR and normalized the augmented contractile responses to norepinephrine but did not alter the contraction to electric field stimulation. Relaxation responses to acetylcholine and sodium nitroprusside were not affected by the treatment. We conclude that a combined treatment with quinapril and atorvastatin lowered blood pressure and improved cardiac and vessel hypertrophy and vessel function. An increase in apoptotic smooth muscle cells may be one of the mechanisms underlying the structural improvement.

  7. Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

    PubMed

    Wach, R; Emery, C J; Bee, D; Barer, G R

    1987-02-01

    The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection

  8. Direct clipping of large basilar trunk aneurysm.

    PubMed

    Kimura, Toshikazu; Nakagawa, Daichi; Kawai, Kensuke

    2015-01-01

    A large basilar trunk aneurysm was incidentally found in a 77-year-old woman in examination for headache. Though it was asymptomatic, high signal intensity was noticed in the brainstem around the aneurysm on FLAIR image of MRI. As she was otherwise healthy, surgical clipping was performed through anterior temporal approach. The video can be found here: http://youtu.be/0soWM8meCW8 . PMID:25554839

  9. Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta.

    PubMed Central

    Cawley, T; Geraghty, J; Osborne, H; Docherty, J R

    1995-01-01

    1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. PMID:7773539

  10. Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

    PubMed

    Newsholme, S J; Thudium, D T; Gossett, K A; Watson, E S; Schwartz, L W

    2000-01-01

    Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.

  11. Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise

    PubMed Central

    Lousinha, Ana; Antunes, Eduardo; Borrecho, Gonçalo; Oliveira, Maria João; Brito, José; Martins dos Santos, José

    2015-01-01

    Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries. Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall-to-perivascular tissue (W/P) ratios were calculated using image J software. Results: There were no differences between exposed and control animals in their L/W ratios (p = 0.687) and time variations in this ratio were non-significant (p = 0.110). In contrast, exposed animals showed lower W/P ratios than control animals (p < 0.001), with significant time variations (p = 0.004). Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis. PMID:25946344

  12. Vasoconstrictor responsiveness of the rat mesenteric arterial bed in cirrhosis.

    PubMed Central

    Ralevic, V.; Mathie, R. T.; Moore, K. P.; Burnstock, G.

    1996-01-01

    1. The effects of cirrhosis on mesenteric vascular reactivity were assessed in constantly perfused mesenteric arterial beds isolated from cirrhotic rats (carbon tetrachloride with phenobarbitone, n = 6), and from phenobarbitone-treated and untreated age-matched controls (n = 4,5). 2. At a constant flow rate of 5 ml min-1 there was no difference in basal perfusion pressure between the groups. Electrical field stimulation (EFS; 4-32 Hz, 90V, 1 ms, 30 s) of perivascular nerves caused frequency-dependent increases in perfusion pressure which were not different between the groups. Dose-dependent vasoconstrictor responses to exogenous noradrenaline (NA), methoxamine (an alpha 1-adrenoceptor agonist), adenosine 5'-triphosphate (ATP) and vasopressin were also similar between the groups. 3. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 microM) augmented constrictor responses to NA, EFS, methoxamine and vasopressin in all groups, and as shown for EFS and NA, this was reversed by L-arginine (300 microM). However, the maximum constrictor responses of cirrhotic preparations in the presence of L-NAME were significantly lower than those of both groups of control animals at the highest frequency of EFS (32 Hz) and highest doses of NA (0.15 and 0.5 mumol) and, compared to phenobarbitone-treated controls, methoxamine (5 mumol). Responses to ATP were significantly augmented by L-NAME only in the cirrhotic group. 4. A step-wise increase in perfusate flow to 10, 15 and 20 ml min-1 produced a broadly similar increase in perfusion pressure within each group. At increased flow rates, cirrhotic preparations were hyporesponsive to NA (15 nmol) compared to the phenobarbitone-treated animals but not the untreated controls. Glibenclamide (5 microM) or L-NAME (30 microM) had no significant effect on the relationship between flow and perfusion pressure or on responses to NA at the different flow rates. 5. We conclude that sympathetic neurotransmission is

  13. Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose

    PubMed Central

    Petit, Marie; Guihot, Anne-Laure; Grimaud, Linda; Vessieres, Emilie; Toutain, Bertrand; Menet, Marie-Claude; Nivet-Antoine, Valérie; Arnal, Jean-François; Loufrani, Laurent; Procaccio, Vincent; Henrion, Daniel

    2016-01-01

    Objectives Chronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats. Methods Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat. Results Arterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups. Conclusion Resveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless

  14. Flow diverter as a rescue therapy for a complicated basilar angioplasty.

    PubMed

    Velioglu, Murat; Ozturk, Ersin; Sonmez, Guner; Kendirli, Tansel; Mutlu, Hakan; Basekim, Cinar

    2013-01-01

    Intracranial atherosclerotic disease is a major cause of ischemic stroke. Stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis was terminated prematurely due to a high stroke and death rate in patients randomized for intracranial stent placement. However, for some patients, angioplasty and/or stent placement remains the best approach. Flow diverters (FDs) are designed to produce a hemodynamic flow diversion by constituting a laminar flow pattern in the parent artery and are mainly used in non-ruptured complex wide-neck aneurysms as well as in ruptured aneurysms. Herein, we present a case where an FD was used in a complicated angioplasty for basilar artery atherosclerosis. A 72-year-old female patient was admitted to our hospital with left side weakness and vertigo. Her diffusion magnetic resonance imaging and magnetic resonance angiography showed right-sided pontine and left-sided occipital acute infarcts with left-sided pontine and right-sided occipital chronic infarcted areas and preocclusive mid-basilar stenosis. The patient was under supervised medical treatment. Despite chronic brain stem and occipital infarcts her modified Rankin Scale was 2. Diagnostic angiography showed no posterior communicating arteries and no pial-pial collaterals and a critical mid-basilar artery stenosis. We decided to perform intracranial angioplasty to increase the perfusion of posterior circulation and reduce the risk of additional embolic infarcts. Angioplasty was complicated with dissection and vessel perforation. We used an FD for rescue therapy to avoid rebleeding. The patient was discharged with good clinical and angiographic results.

  15. Estrogen replacement increases beta-adrenoceptor-mediated relaxation of rat mesenteric arteries.

    PubMed

    Ferrer, M; Meyer, M; Osol, G

    1996-01-01

    The purpose of the present study was to determine whether estrogen replacement in ovariectomized rats could modulate arterial diameter responses to beta-adrenoceptor activation. Under relaxed conditions (0.1 mM papaverine) there were no differences in the lumen diameter of isolated, pressurized (50 mm Hg) mesenteric arteries from nontreated (191.7 +/- 13.8 microns; n = 19) versus those from estrogen-treated (190.1 +/- 11 microns; n = 14) ovariectomized Sprague-Dawley rats. In arteries precontracted with noradrenaline (0.3-1 microM), isoprenaline (0.01-10 microM)-induced relaxation was significantly increased in arteries from ovariectomized estrogen-treated rats (52.4 +/- 2% of the maximal relaxation induced by 0.1 mM papaverine, vs. 33.3 +/- 6.5%; p < 0.01). The half-maximal concentration value was 0.04 +/- 0.05 microM in estrogen-treated rats and 0.4 +/- 0.1 microM in nontreated rats (p < 0.01). This response was inhibited by propranolol (1 microM) in both groups to a comparable extent (61.5%), and was unaffected by endothelial removal. Forskolin (0.01-10 microM) induced similar concentration-dependent vasodilation in arteries of both groups of rats with no differences in sensitivity or maximal response. These results suggest that isoprenaline acts through beta-adrenoceptors present on vascular smooth muscle and that estrogen replacement enhances the relaxant responses induced by beta-adrenoceptor activation by an endothelium-independent mechanism.

  16. Contribution of the vertebral artery to cerebral circulation in the rat snake Elaphe obsoleta

    NASA Technical Reports Server (NTRS)

    Zippel, K. C.; Lillywhite, H. B.; Mladinich, C. R.; Hargens, A. (Principal Investigator)

    1998-01-01

    Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing.

  17. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

    PubMed

    Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

    2015-11-01

    Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.

  18. Regeneration of the rat carotid artery after clipping injury. Part I. A morphological study.

    PubMed

    Tsukahara, T; Yonekawa, Y; Yamamoto, M; Kaku, Y; Ogata, N; Taniguchi, T

    1993-01-01

    We investigated the natural course of the morphological regeneration of the endothelium and smooth muscle of the rat carotid artery after clipping injury. Vascular damage was produced by clipping the right carotid arteries of Wistar rats. Endothelial regeneration was confirmed by the injection of Evans blue dye and the detection of factor VIII-related antigen. The volume of the smooth muscle cell layer and the luminal size were measured by computer-assisted morphometric analysis. Immediately after arterial injury, Evans blue dye freely permeated the smooth muscle layer, suggesting that complete endothelial denudation had occurred. Endothelial regrowth started within 24 hours and was fastest on the third and fourth days after injury. The endothelial injury was repaired within 5 days. The area of the smooth muscle layer did not change immediately after clipping injury, but it gradually increased within a month. The luminal area of the injured artery increased during the 3-month recovery period. These findings suggest that endothelial regrowth is completed within a week after clipping injury, whereas smooth muscle cell regrowth is slower. In addition, arteriosclerotic luminal narrowing did not occur during recovery of the rat carotid artery from clipping injury.

  19. Effects of glucagon-like peptide-1 in diabetic rat small resistance arteries.

    PubMed

    Bayram, Zeliha; Nacitarhan, Cahit; Ozdem, Sadi S

    2014-09-01

    We investigated the functional effects of glucagon-like peptide-1 [GLP-1(7-36)] and GLP-1(9-36) and the mechanism(s) playing a role in the effects of these agents in isolated small resistance arteries from control and diabetic rats. Cumulative concentrations of GLP-1(7-36) and GLP-1(9-36) produced concentration-dependent relaxations in endothelium-intact but not endothelium-denuded arteries that were significantly decreased in diabetic rats. GLP-1 receptor antagonist exendin(9-39) significantly inhibited responses to GLP-1 analogs. Nitric oxide/cyclic guanosine monophosphate pathway blockers, but not indomethacin, significantly decreased responses to GLP-1(7-36) or GLP-1(9-36) in control and diabetic rats. 4-Aminopyridine or glibenclamide incubation did not alter relaxations to GLP-1 analogs. GLP-1(7-36)- and GLP-1(9-36)-induced relaxations were blunted significantly and to similar extends by charybdotoxin and apamin combination in control and diabetic rats. Catalase did not affect, whereas superoxide dismutase (SOD) caused a significant increase in relaxations to GLP-1 analogs only in diabetic rats. We provided evidence about the relaxant effects of GLP-1(7-36) and GLP-1(9-36) in resistance arteries that were reduced in diabetic rats. Both calcium-activated potassium channels and endothelium played a major role in relaxations. Increment in certain reactive oxygen species and/or reduction in superoxide dismutase function might play a role in reduced relaxant responses of resistance arteries to GLP-1(7-36) and GLP-1(9-36) in diabetic rats.

  20. Histamine H1-receptors mediate endothelium-dependent relaxation of rat isolated pulmonary arteries.

    PubMed

    Szarek, J L; Bailly, D A; Stewart, N L; Gruetter, C A

    1992-01-01

    Histamine has been reported to cause endothelium-dependent relaxation of vascular smooth muscle and vasodilation. This study was undertaken to examine the inhibitory effects of histamine on cylindrical segments of extrapulmonary arteries isolated from male Sprague Dawley rats. In arterial segments precontracted with phenylephrine (10 microM), histamine (0.1-100 microM) elicited concentration-dependent relaxation responses. Removal of the endothelium or pretreatment with methylene blue (10 microM) abolished relaxation responses to low concentrations of histamine and markedly inhibited those caused by histamine at concentrations greater than 1 microM. Incubation of endothelium-intact arterial segments with pyrilamine (1 microM) caused a significant rightward shift of the histamine concentration-response curves. Treatment of the segments with cimetidine (100 microM) or indomethacin (10 microM) only minimally antagonized histamine-induced relaxation in arteries with endothelium. Residual relaxation responses observed in arteries stripped of endothelium were unaffected by pretreatment with cimetidine, indomethacin, or pyrilamine. The results suggest that the inhibitory effect of histamine in rat pulmonary arteries is mediated predominantly by activation of H1-receptors on the endothelium and the subsequent release of endothelium-derived relaxing factor(s).

  1. Regulation of vascular tone by UTP and UDP in isolated rat intrapulmonary arteries.

    PubMed

    Rubino, A; Ziabary, L; Burnstock, G

    1999-04-01

    Vasoconstrictor and vasodilator responses of isolated rat intrapulmonary arteries to the pyrimidine nucleotides UTP and UDP were evaluated and compared with vascular responses to ATP and its analogues. UTP and UDP (1-500 microM) were equipotent in inducing concentration-dependent vasoconstriction, unaffected by the P2 receptor antagonists suramin (100 microM) and Reactive blue 2 (50 microM); ATP (10-500 microM) produced weaker vasoconstriction. UTP and UDP lacked vasodilator activity, while ATP and its analogue 2-methylthio ATP evoked endothelium-dependent vasodilatation. These results indicate that UTP and UDP evoke vasoconstriction of rat intrapulmonary arteries whereas ATP is predominantly a vasodilator at the same arteries. Furthermore, the pharmacological profile of the native UTP/UDP receptor differs from that of the known P2Y2, P2Y4 and P2Y6 recombinant receptors for pyrimidine nucleotides.

  2. Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls

    PubMed Central

    Johnson, Kyle B.; Hitomi, Kiyotaka; Tykocki, Nathan R.; Thompson, Janice M.; Watts, Stephanie W.

    2015-01-01

    Transglutaminases (TGs) catalyze the formation of covalent cross-links between glutamine residues and amine groups. This cross-linking activity has been implicated in arterial remodeling. Because hypertension is characterized by arterial remodeling, we hypothesized that TG activity, expression, and functionality would be increased in the aorta, but not in the vena cava (which does not undergo remodeling), from hypertensive rats relative to normotensive rats. Spontaneously hypertensive stroke-prone rats (SHRSP) and DOCA-salt rats as well as their respective normotensive Wistar-Kyoto or Sprague-Dawley counterparts were used. Immunohistochemistry and Western blot analysis measured the presence and expression of TG1 and TG2, in situ activity assays quantified active TGs, and isometric contractility was used to measure TG functionality. Contrary to our hypothesis, the activity (52% DOCA-salt vs. control rats and 56% SHRSP vs. control rats, P < 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P > 0.05, and TG2: 77% DOCA-salt vs. control rats, P < 0.05), and functionality of TG1 and TG2 were decreased in the aorta, but not in the vena cava, from hypertensive rats. Mass spectrometry identified proteins uniquely amidated by TGs in the aorta that play roles in cytoskeletal regulation, redox regulation, and DNA/RNA/protein synthesis and regulation and in the vena cava that play roles in cytoskeletal regulation, coagulation regulation, and cell metabolism. Consistent with the idea that growing cells lose TG2 expression, vascular smooth muscle cells placed in culture lost TG2 expression. We conclude that the expression, activity, and functionality of TG1 and TG2 are decreased in the aorta, but not in the vena cava, from hypertensive rats compared with control rats. PMID:25599570

  3. Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

    PubMed Central

    Chen, Yulong; Xu, Cangbao; Wei, Yahui; Zhang, Yaping; Cao, Ailan

    2016-01-01

    Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97.66±0.79%; pD2, 4.30±0.14) or KCl (Emax, 101.3±0.6%; pD2, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. NG-nitro-L-arginine methyl ester (100 µM) significantly inhibited the Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (10 µM) and indomethacin (5 µM) each had no effect on the Res-induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4-aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca2+-free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release, and also through an endothelium-independent pathway, with opening of voltage-dependent K+ channels and ATP-sensitive K+ channels and blockade of extracellular Ca2+ influx. PMID:27698719

  4. Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

    PubMed Central

    Chen, Yulong; Xu, Cangbao; Wei, Yahui; Zhang, Yaping; Cao, Ailan

    2016-01-01

    Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97.66±0.79%; pD2, 4.30±0.14) or KCl (Emax, 101.3±0.6%; pD2, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. NG-nitro-L-arginine methyl ester (100 µM) significantly inhibited the Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (10 µM) and indomethacin (5 µM) each had no effect on the Res-induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4-aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca2+-free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release, and also through an endothelium-independent pathway, with opening of voltage-dependent K+ channels and ATP-sensitive K+ channels and blockade of extracellular Ca2+ influx.

  5. Fasudil evokes vasodilatation of rat mesenteric vascular bed via Ca(2+) channels and Rho/ROCK pathway.

    PubMed

    Chen, Yu-Cai; Yuan, Tian-Yi; Zhang, Hui-Fang; Wang, Dan-Shu; Niu, Zi-Ran; Li, Li; Fang, Lian-Hua; Du, Guan-Hua

    2016-10-01

    As a Rho kinase (ROCK) inhibitor, fasudil has been used in clinical trials of several cardiovascular diseases. This study was to investigate the vasorelaxant effect of fasudil on resistance arterial rings including mesenteric, renal, ventral tail and basilar artery. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings. A DMT multiwire myograph system was used to test the tension of isolated small arteries. K(+) channel blockers, NO-cGMP pathway blockers and Ca(2+)-free physiological salt solution (PSS) were employed to verify the underlying mechanisms. Fasudil (10(-7)-10(-4)M) relaxed four types of small artery rings pre-contracted by 60mmol/l KCl (pEC50: 6.01±0.09, 5.47±0.03, 5.54±0.04, and 5.72±0.10 for mesenteric, renal, ventral tail and basilar artery rings, respectively). Pre-incubation with fasudil (1, 3, or 10μmol/l) attenuated KCl (10-60mmol/l) and angiotensin II (Ang II; 1μmol/l)-induced vasoconstriction in mesenteric artery rings. Fasudil at the concentration of 10(-6)mol/l showed different relaxant potency in endothelium intact (pEC50:6.01±0.09) or denued (5.75±0.06) mesenteric artery. The influx and release of Ca(2+) were inhibited by fasudil. In addition, fasudil could block the increased phosphorylation level of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by Ang II. However, pretreatment with various K(+) channel blockers did not affect the relaxant effects of fasudil remarkably. The present results demonstrate that fasudil has a vasorelaxant effect on isolated rat resistance arteries, including mesenteric, renal, ventral tail and basilar artery, and may exert its action through the endothelium, Ca(2+) channels, and the Rho/ROCK pathway. PMID:27346833

  6. Fasudil evokes vasodilatation of rat mesenteric vascular bed via Ca(2+) channels and Rho/ROCK pathway.

    PubMed

    Chen, Yu-Cai; Yuan, Tian-Yi; Zhang, Hui-Fang; Wang, Dan-Shu; Niu, Zi-Ran; Li, Li; Fang, Lian-Hua; Du, Guan-Hua

    2016-10-01

    As a Rho kinase (ROCK) inhibitor, fasudil has been used in clinical trials of several cardiovascular diseases. This study was to investigate the vasorelaxant effect of fasudil on resistance arterial rings including mesenteric, renal, ventral tail and basilar artery. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings. A DMT multiwire myograph system was used to test the tension of isolated small arteries. K(+) channel blockers, NO-cGMP pathway blockers and Ca(2+)-free physiological salt solution (PSS) were employed to verify the underlying mechanisms. Fasudil (10(-7)-10(-4)M) relaxed four types of small artery rings pre-contracted by 60mmol/l KCl (pEC50: 6.01±0.09, 5.47±0.03, 5.54±0.04, and 5.72±0.10 for mesenteric, renal, ventral tail and basilar artery rings, respectively). Pre-incubation with fasudil (1, 3, or 10μmol/l) attenuated KCl (10-60mmol/l) and angiotensin II (Ang II; 1μmol/l)-induced vasoconstriction in mesenteric artery rings. Fasudil at the concentration of 10(-6)mol/l showed different relaxant potency in endothelium intact (pEC50:6.01±0.09) or denued (5.75±0.06) mesenteric artery. The influx and release of Ca(2+) were inhibited by fasudil. In addition, fasudil could block the increased phosphorylation level of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by Ang II. However, pretreatment with various K(+) channel blockers did not affect the relaxant effects of fasudil remarkably. The present results demonstrate that fasudil has a vasorelaxant effect on isolated rat resistance arteries, including mesenteric, renal, ventral tail and basilar artery, and may exert its action through the endothelium, Ca(2+) channels, and the Rho/ROCK pathway.

  7. [CHANGES IN THE METABOLISM IN THE MYOCARDIUM OF RATS WITH ARTERIAL HYPERTENSION].

    PubMed

    Dovgan, R S; Zagorodnyi, M I

    2015-01-01

    In the myocardium of the rats with arterial hypertension marked increase in the amount of unsaturated fatty acids and polyunsaturated fatty acids. Reducing the concentration of palmitic acid and increased levels of arachidonic acid is considered as one of the factors that lead to the development of energy deficit and oxidative stress. In rats, with hypertension myocardial lactate concentration increases in the cytoplasmic fraction and reducing the amount of ATP. The level in the cytoplasmic and mitochondrial fractions above benchmarks, indicating about the change of antioxidant systems of the body In the cytoplasm and mitochondria of cardiomyocytes of the rats with arterial hypertension marked decrease in the activity of antioxidant enzymes: NO-synthase, catalase, glutathione reductase, which causes metabolic changes of the myocardium. PMID:27491168

  8. Impaired Ca2+ handling in penile arteries from prediabetic Zucker rats: involvement of Rho kinase.

    PubMed

    Villalba, Nuria; Contreras, Cristina; Hernández, Medardo; García-Sacristán, Albino; Prieto, Dolores

    2011-06-01

    Diabetes is associated with an increased vascular tone usually involved in the pathogenesis of diabetic cardiovascular complications such as hypertension, stroke, coronary artery disease, or erectile dysfunction (ED). Enhanced contractility of penile erectile tissue has been associated with augmented activity of the RhoA/Rho kinase (RhoK) pathway in models of diabetes-associated ED. The present study assessed whether abnormal vasoconstriction in penile arteries from prediabetic obese Zucker rats (OZRs) is due to changes in the intracellular Ca(2+) concentration ([Ca(2+)](i)) and/or in myofilament Ca(2+) sensitivity. Penile arteries from OZRs and lean Zucker rats (LZRs) were mounted on microvascular myographs for simultaneous measurements of [Ca(2+)](i) and tension. The relationships between [Ca(2+)](i) and contraction for the α(1)-adrenergic vasoconstrictor phenylephrine (PE) were left shifted and steeper in OZRs compared with LZRs, although the magnitude of the contraction was similar in both groups. In contrast, the vasoconstriction induced by the thromboxane A(2) receptor agonist U-46619 was augmented in arteries from OZRs, and this increase was associated with an increase in both the sensitivity and maximum responses to Ca(2+). The RhoK inhibitor Y-27632 (10 μM) reduced the vasoconstriction induced by PE to a greater extent in OZRs than in LZRs, without altering Ca(2+). Y-27632 inhibited with a greater potency the contraction elicited by high KCl in arteries from OZRs compared with LZRs without changing [Ca(2+)](i). RhoK-II expression was augmented in arteries from OZRs. These results suggest receptor-specific changes in the Ca(2+) handling of penile arteries under conditions of metabolic syndrome. Whereas augmented vasoconstriction upon activation of the thromboxane A(2) receptor is coupled to enhanced Ca(2+) entry, a RhoK-mediated enhancement of myofilament Ca(2+) sensitivity is coupled with the α(1)-adrenergic vasoconstriction in penile arteries from OZRs.

  9. Basilar Fracture Due to Frozen Corpse: A Case Report.

    PubMed

    Zhang, Junchao; Yan, Yibo; Chen, Yiqun; Huang, Sizhe; Liu, Liang

    2016-09-01

    Basilar fractures are one of the consequences of craniocerebral injury, which is serious enough to cause death. Legal examiners often pay attention to basilar fractures at autopsy and analyze the relationship between them and death. It is noteworthy whether the fracture is premortem or postmortem. Here, we describe a rarely reported case of basilar fracture due to freezing. In this case, a 30-year-old man was frozen (-18°C) for 6 months after death. At autopsy, external examination showed no trauma. However, on internal examination, there was a basilar fracture which caused controversy but turned out to be a postmortem injury. We provide the case description and discussion on antemortem or postmortem basilar fractures as a differential for these cases. PMID:27400253

  10. Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries.

    PubMed

    Li, Rachel Wai-Sum; Yang, C; Shan, Luchen; Zhang, Zaijun; Wang, Yuqiang; Kwan, Y W; Lee, Simon M Y; Hoi, Maggie P M; Chan, S W; Cheung, Alex Chun; Cheung, K H; Leung, George P H

    2015-08-15

    Danshen (Radix Salviae miltiorrhizae) and ChuanXiong (Ligusticum wallichii) are two traditional herbal medicines commonly used in China for the treatment of cardiovascular diseases. The active components in Danshen and ChuanXiong are Danshensu (DSS, (R)-3, 4-dihydroxyphenyllactic acid) and tetramethylpyrazine (TMP), respectively. In the present study, a new compound named ADTM, which is a conjugation of DSS and TMP, was synthesized and its effect on the contractility of rat mesenteric arteries was examined. The relaxation effect of ADTM on rat mesenteric arteries was studied using myography. The effects of ADTM on Ca(2+) channels were measured by Ca(2+) imaging and patch-clamp techniques. The results showed that ADTM caused a concentration-dependent relaxation of rat mesenteric arteries. This relaxation effect was not affected by the removal of endothelium or inhibitors of nitric oxide synthase, cyclooxygenase, guanylyl cyclase and adenylyl cyclase. Potassium channel blockers including tetraethylammonium, iberiotoxin, apamin, 4-aminopyridine, BaCl2 and glibenclamide also failed to inhibit the relaxation response to ADTM. ADTM inhibited CaCl2-induced contractions and reduced the Ca(2+) influx in isolated mesenteric arterial muscle cells. Our results suggest that ADTM may be a novel relaxing agent. Its mechanism of action involves the direct blockade of voltage-gated Ca(2+) channels in vascular smooth muscle cells, resulting in a decrease in Ca(2+) influx into the cells. PMID:25952729

  11. Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring.

    PubMed

    Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; de Leeuw, Peter W; Blanco, Carlos E; De Mey, Jo G R

    2004-06-01

    Fetal malnutrition and hypoxia may modify organ system maturation and result in cardiovascular diseases in the adult. We tested whether intrauterine stress (IUS) leads to persistent alterations of renal biology. In rats, intrauterine stress was induced by ligation of the uterine arteries at day 17 of pregnancy. Renal arteries of the 21-day-old male offspring were isolated to study pharmacological reactivity. Kidneys were dissected to analyze renal structure and beta-adrenoceptor expression. At 21 days of age, half of the animals underwent unilateral left nephrectomy. At the age of 12 weeks, rats were instrumented for blood pressure monitoring, blood sampling, and renal function measurements. After IUS, litter size and birth weight were reduced, whereas the hematocrit was increased. Renal arterial responses to beta-adrenergic stimulation and sensitivity to adenylyl cyclase activation were increased, along with the renal expression of beta2-adrenoceptors. At 21 days and at 6 months of age, the number and density of the glomeruli were reduced, whereas their size was increased. The filtration fraction and urinary albumin concentration were increased 12 weeks after intrauterine stress. In control rats, removal of the left kidney at 21 days of age did not affect kidney function and blood pressure. However, after IUS, the remaining right kidney failed to compensate for the loss of the left kidney, and blood pressure was increased. In conclusion, prenatal stress transiently modifies renal arterial reactivity and results in long-lasting adverse effects on renal structure and function and on renal compensatory mechanisms. PMID:15117909

  12. Effects of vascular constriction on occlusive thrombus formation of rat mesenteric artery.

    PubMed

    Araki, H; Nishi, K

    1986-10-01

    Effects of vascular constriction on thrombotic occlusion was evaluated using rat mesenteric arteries and video-recording system attached to the microscope. Topical application of norepinephrine of 1, 10 and 100 micrograms/ml reduced the arterial diameter dose dependently from 297 +/- 41 mu to 166 +/- 50, 87 +/- 18 and 84 +/- 11 mu (mean +/- SD, n = 7), respectively. The diameter reduction by the higher 2 doses persisted for more than 30 minutes until the wash out of the agent. But, no thrombus formation was observed. A reproducible thrombus formation was induced by inserting a glass micropipette into the vascular lumen. The maximal percent occlusion by the thrombus was 80 +/- 11% (range; 67 to 95%, n = 7). The topical application of 10 micrograms/ml norepinephrine induced vasoconstriction and increased the percent occlusion significantly to 97 +/- 8% (p less than 0.05). Complete occlusion of the lumen developed in 6 of 7 rats after the agent and in 2 rats it was not released until the wash out of the agent for more than 30 minutes. Thrombus formation itself did not change the arterial diameter at the site of thrombus formation as well as at sites of 300 and 600 mu down stream. It is suggested that the vascular constriction alone does not necessarily cause thrombus formation but may aggravate the arterial flow reduction induced by thrombosis.

  13. 4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Long, Mei; Wang, Jie; Liu, Fen; Gai, Min-Tao; Aierken, Alidan; Li, Ming-Yuan; Li, Qian; Wu, Lei-Qi; Ma, Yi-Tong; Hujiaaihemaiti, Minawaer

    2016-01-01

    Background Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Methods and Results Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Conclusion Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries. PMID:27304885

  14. Role of Elastin in Spontaneously Hypertensive Rat Small Mesenteric Artery Remodelling

    PubMed Central

    Briones, Ana M; González, José M; Somoza, Beatriz; Giraldo, Jesús; Daly, Craig J; Vila, Elisabet; Carmen González, M; McGrath, John C; Arribas, Silvia M

    2003-01-01

    Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate the role of elastin in vascular remodelling of mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments from Wistar Kyoto rats (WKY) and SHR were pressurised under passive conditions at a range of physiological pressures with pressure myography. Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure-fixed arteries. To assess the contribution of elastin to MRA structure and mechanics, myograph-mounted vessels were studied before and after elastase incubation. When compared with WKY, MRA from SHR showed: (1) a smaller lumen, (2) decreased distensibility at low pressures, (3) a leftward shift of the stress-strain relationship, (4) redistribution of elastin within the internal elastic lamina (IEL) leading to smaller fenestrae but no change in fenestrae number or elastin amount. Elastase incubation (1) fragmented the structure of IEL in a concentration-dependent fashion, (2) abolished all the structural and mechanical differences between strains, and (3) decreased distensibility at low pressures. The study shows the overriding role of elastin in determining vascular dimensions and mechanical properties in a resistance artery. In addition, it informs hypertensive remodelling. MRA remodelling and increased stiffness are accompanied by elastin restructuring within the IEL and elastin degradation reverses structural and mechanical alterations of SHR MRA. Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension. PMID:12844513

  15. Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats.

    PubMed Central

    Batalha, Joao R F; Saldiva, Paulo H N; Clarke, Robert W; Coull, Brent A; Stearns, Rebecca C; Lawrence, Joy; Murthy, G G Krishna; Koutrakis, Petros; Godleski, John J

    2002-01-01

    The objective of this study was to determine whether short-term exposures to concentrated ambient particles (CAPs) alter the morphology of small pulmonary arteries in normal rats and rats with chronic bronchitis (CB). Sprague-Dawley male rats were exposed to CAPs, using the Harvard Ambient Particle Concentrator, or to particle-free air (sham) under identical conditions during 3 consecutive days (5 hr/day) in six experimental sets. CB was induced by exposure to 276 +/- 9 ppm of sulfur dioxide (5 hr/day, 5 days/week, 6 weeks). Physicochemical characterization of CAPs included measurements of particle mass, size distribution, and composition. Rats were sacrificed 24 hr after the last CAPs exposure. Histologic slides were prepared from random sections of lung lobes and coded for blinded analysis. The lumen/wall area (L/W) ratio was determined morphometrically on transverse sections of small pulmonary arteries. When all animal data (normal and CB) were analyzed together, the L/W ratios decreased as concentrations of fine particle mass, silicon, lead, sulfate, elemental carbon, and organic carbon increased. In separate univariate analyses of animal data, the association for sulfate was significant only in normal rats, whereas silicon was significantly associated in both CB and normal rats. In multivariate analyses including all particle factors, the association with silicon remained significant. Our results indicate that short-term CAPs exposures (median, 182.75 micro g/m3; range, 73.50-733.00 micro g/m3) can induce vasoconstriction of small pulmonary arteries in normal and CB rats. This effect was correlated with specific particle components and suggests that the pulmonary vasculature might be an important target for ambient air particle toxicity. PMID:12460797

  16. Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. I. Impact of obesity.

    PubMed

    Jenkins, Nathan T; Padilla, Jaume; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Davis, J Wade; Laughlin, M Harold

    2014-04-15

    We employed next-generation RNA sequencing (RNA-Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133 downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA [false discovery rate (FDR) < 10%] with an overlap of 93 genes between the arteries. In LETO rats, there were 89 upregulated and 114 downregulated genes in the GFA compared with the SFA. There were 244 upregulated and 275 downregulated genes in OLETF rats (FDR < 10%) in the GFA compared with the SFA, with an overlap of 76 differentially expressed genes common to both LETO and OLETF rats in both the GFA and SFA. A total of 396 transcripts were found to be differentially expressed between LETO and OLETF in aortic endothelial cell-enriched samples. Overall, we found 1) the existence of heterogeneity in the transcriptional profile of the SFA and GFA within healthy LETO rats, 2) that this between-vessel heterogeneity was markedly exacerbated in the hyperphagic, obese OLETF rat, and 3) a greater number of genes whose expression was altered by obesity in the SFA compared with the GFA. Also, results indicate that in OLETF rats the GFA takes on a relatively more proatherogenic phenotype compared with the SFA.

  17. Transfundal stent placement for treatment of complex basilar tip aneurysm: technical note

    PubMed Central

    Vasquez, Ciro; Hubbard, Molly; Jagadeesan, Bharathi Dasan; Tummala, Ramachandra Prasad

    2014-01-01

    We describe a case where a complex unruptured basilar tip aneurysm was treated with a unique method of stent-assisted coil embolization. The aneurysm was considered to have a complex anatomy since both the left posterior cerebral artery and left superior cerebellar artery originated from the dome of the aneurysm. Also, the right posterior cerebral artery was incorporated in the aneurysm neck and needed to be protected prior to coil embolization. This case describes placement of a stent across the span of the aneurysm fundus in order to preserve the two branches arising from it, and the aneurysm dome was coiled without any complication. Using modifications of existing strategies for stent-assisted coil embolization, the aneurysm was treated without any complications and all of the vessels at risk were preserved. PMID:25336546

  18. Long-term outcome of basilar stenosis in Erdheim–Chester disease

    PubMed Central

    Mathis, Stéphane; Godenèche, Gaëlle; Haroche, Julien; Milin, Serge; Julian, Adrien; Berthomet, Aline; Baron, Clément; Palazzo, Paola; Neau, Jean-Philippe

    2016-01-01

    Abstract Background: Erdheim–Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. This inflammatory myeloid neoplasm is frequently complicated by neurological symptoms, but stroke is an exceptional manifestation of this disease. Methods: We report the case of a 59-year-old woman who presented a vertebrobasilar stroke secondary to infiltration and severe stenosis of the basilar artery, improved after interferon-alpha therapy. We performed a review of the relevant literature and reported the few other cases described. Results: With our patient, we have found only 7 observations of cerebrovascular disorder in ECD. Most of them had supravascular arteries involvement. Conclusion: Stroke is a rare treatable and potentially reversible complication of ECD. The pathophysiological processes explaining stroke in this disease are uncertain, but periarterial stenosis of cerebral arteries may be a mechanism. PMID:27603396

  19. Transfundal stent placement for treatment of complex basilar tip aneurysm: technical note.

    PubMed

    Vasquez, Ciro; Hubbard, Molly; Jagadeesan, Bharathi Dasan; Tummala, Ramachandra Prasad

    2015-10-01

    We describe a case where a complex unruptured basilar tip aneurysm was treated with a unique method of stent-assisted coil embolization. The aneurysm was considered to have a complex anatomy since both the left posterior cerebral artery and left superior cerebellar artery originated from the dome of the aneurysm. Also, the right posterior cerebral artery was incorporated in the aneurysm neck and needed to be protected prior to coil embolization. This case describes placement of a stent across the span of the aneurysm fundus in order to preserve the two branches arising from it, and the aneurysm dome was coiled without any complication. Using modifications of existing strategies for stent-assisted coil embolization, the aneurysm was treated without any complications and all of the vessels at risk were preserved.

  20. Differential remodeling of carotid artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats.

    PubMed

    Cebová, M; Kristek, F; Kunes, J

    2006-01-01

    High blood pressure, increased level of cholesterol, diabetes, hypertriglyceridemia and obesity are risk factors accompanied metabolic syndrome. The aim of the study was to compare geometry of carotid artery (AC) of 3-week-old (3w) and 52-week-old (52w) hereditary hypertriglyceridemic rats (hHTG) and spontaneously hypertensive rats (SHR) which represent a genetic model of human essential hypertension with age-matched Wistar rats. After sacrificing the rats were perfused with a glutaraldehyde fixative under the pressure 90 mm Hg (3w) and 120 mm Hg (52w) for 10 min via cannula placed into left ventricle. Middle part of AC was excised and processed according to standard electron microscopy procedure. Geometry of AC was evaluated in light microscopy. SHR vs. Wistar rats: BP of 3w did not differ, in 52w it was increased; cardiac hypertrophy was found in both ages; wall thickness (WT) and cross sectional area (CSA) in 3w did not differ, in 52w both were increased; inner diameter (ID) in 3w and 52w was decreased; WT/ID was increased in both ages. Hereditary HTG vs. Wistar rats: BP was increased in both periods; cardiac hypertrophy was observed in 3w; WT in 3w was decreased, in 52w it was increased; CSA and ID were decreased in both ages; WT/ID was increased only in 52w. Discrepancies between development of BP, cardiac hypertrophy in SHR and hHTG rats were observed. Alterations of BP were not in harmony with alterations in geometry of carotid arteries in both SHR and hHTG rats. We suggest that BP is not the main stimuli evoked hemodynamic and structural alterations of cardiovascular system in ontogenic development of SHR and hHTG rats.

  1. Failure of atriopeptin II to cause arterial vasodilation in the conscious rat.

    PubMed

    Lappe, R W; Smits, J F; Todt, J A; Debets, J J; Wendt, R L

    1985-04-01

    The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Cardioprotective effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats.

    PubMed

    Gao, Yan; Gao, Jianping; Chen, Changxun; Wang, Huilin; Guo, Juan; Wu, Rong

    2015-05-01

    The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation.

  3. Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial dysfunction of pulmonary arteries in rats.

    PubMed

    Wang, Zhuo; Li, Ai-Ying; Guo, Qiu-Hong; Zhang, Jian-Ping; An, Qi; Guo, Ya-jing; Chu, Li; Weiss, J Woodrow; Ji, En-Sheng

    2013-01-01

    Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disorders and in some cases is complication of pulmonary hypertension. We simulated OSA by exposing rats to cyclic intermittent hypoxia (CIH) to investigate its effect on pulmonary vascular endothelial dysfunction. Sprague-Dawley Rats were exposed to CIH (FiO2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/wk for 3 wk), and the pulmonary arteries of normoxia and CIH treated rats were analyzed for expression of endothelin-1 (ET-1) and ET receptors by histological, immunohistochemical, RT-PCR and Western Blot analyses, as well as for contractility in response to ET-1. In the pulmonary arteries, ET-1 expression was increased, and ET-1 more potently elicited constriction of the pulmonary artery in CIH rats than in normoxic rats. Exposure to CIH induced marked endothelial cell damage associated with a functional decrease of endothelium-dependent vasodilatation in the pulmonary artery. Compared with normoxic rats, ETA receptor expression was increased in smooth muscle cells of the CIH rats, while the expression of ETB receptors was decreased in endothelial cells. These results demonstrated endothelium-dependent vasodilation was impaired and the vasoconstrictor responsiveness increased by CIH. The increased responsiveness to ET-1 induced by intermittent hypoxia in pulmonary arteries of rats was due to increased expression of ETA receptors predominantly, meanwhile, decreased expression of ETB receptors in the endothelium may also participate in it.

  4. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.

    PubMed

    Drexler, E S; Bischoff, J E; Slifka, A J; McCowan, C N; Quinn, T P; Shandas, R; Ivy, D D; Stenmark, K R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  5. Copper Dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans

    PubMed Central

    Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A.; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C.; Humbert, Marc; Noordegraaf, Anton Vonk; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F.

    2012-01-01

    Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation–induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide–1 inhibition or lysyl–oxidase–1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension. PMID:22162909

  6. Reticular lamina and basilar membrane vibrations in living mouse cochleae.

    PubMed

    Ren, Tianying; He, Wenxuan; Kemp, David

    2016-08-30

    It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar membrane vibrations, yet how cellular forces amplify vibrations is poorly understood. In this study, by measuring subnanometer vibrations directly from the reticular lamina at the apical ends of outer hair cells and from the basilar membrane using a custom-built heterodyne low-coherence interferometer, we demonstrate in living mouse cochleae that the sound-induced reticular lamina vibration is substantially larger than the basilar membrane vibration not only at the best frequency but surprisingly also at low frequencies. The phase relation of reticular lamina to basilar membrane vibration changes with frequency by up to 180 degrees from ∼135 degrees at low frequencies to ∼-45 degrees at the best frequency. The magnitude and phase differences between reticular lamina and basilar membrane vibrations are absent in postmortem cochleae. These results indicate that outer hair cells do not amplify the basilar membrane vibration directly through a local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration collaboratively interacts with the basilar membrane traveling wave primarily through the cochlear fluid, which boosts peak responses at the best-frequency location and consequently enhances hearing sensitivity and frequency selectivity. PMID:27516544

  7. Reticular lamina and basilar membrane vibrations in living mouse cochleae.

    PubMed

    Ren, Tianying; He, Wenxuan; Kemp, David

    2016-08-30

    It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar membrane vibrations, yet how cellular forces amplify vibrations is poorly understood. In this study, by measuring subnanometer vibrations directly from the reticular lamina at the apical ends of outer hair cells and from the basilar membrane using a custom-built heterodyne low-coherence interferometer, we demonstrate in living mouse cochleae that the sound-induced reticular lamina vibration is substantially larger than the basilar membrane vibration not only at the best frequency but surprisingly also at low frequencies. The phase relation of reticular lamina to basilar membrane vibration changes with frequency by up to 180 degrees from ∼135 degrees at low frequencies to ∼-45 degrees at the best frequency. The magnitude and phase differences between reticular lamina and basilar membrane vibrations are absent in postmortem cochleae. These results indicate that outer hair cells do not amplify the basilar membrane vibration directly through a local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration collaboratively interacts with the basilar membrane traveling wave primarily through the cochlear fluid, which boosts peak responses at the best-frequency location and consequently enhances hearing sensitivity and frequency selectivity.

  8. Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

    PubMed

    Vaskonen, T; Mervaala, E; Nevala, R; Soots, A; Krogerus, L; Lähteenmäki, T; Karppanen, H; Vapaatalo, H; Ahonen, J

    2000-01-01

    The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

  9. Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery occluded rat

    PubMed Central

    Akhtar, Mohammad; Maikiyo, Aliyu Muhammad; Khanam, Razia; Mujeeb, Mohd; Aqil, Mohd; Najmi, Abul Kalam

    2012-01-01

    Purpose: Aqueous and hydroalcoholic extracts of Nigella sativa (400 mg/kg, orally) for 7 days were administered and evaluated for their neuroprotective effects on middle cerebral artery occluded (MCAO) rats. Materials and Methods: Cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion for 22 h. After 24 h of ischemia, grip strength, locomotor activity tests were performed in the surgically operated animals. After behavioral tests, animals were immediately sacrificed. Infarct volumes followed by the estimation of markers of oxidative stress in the brains were measured. Results: Locomotor activity and grip strength of animals were improved in both aqueous and hydroalcoholic extracts pretreated rats. Infarct volume was also reduced in both extracts pretreated rats as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione and antioxidant enzymes, viz., superoxide dismutase (SOD) and catalase levels were observed following MCAO. Pretreatment of Nigella sativa extracts showed the reduction in TBARS, elevation in glutathione, SOD and catalase levels as compared with MCAO rats. Conclusion: The present study observed the neuroprotective effects of both the extracts of Nigella sativa in cerebral ischemia. The neuroprotective effects could be due to its antioxidant, free radical scavenging, and anti-inflammatory properties. PMID:22368403

  10. Relation between peripheral chemoreceptors stimulation and pulmonary arterial blood pressure in rats.

    PubMed

    Lagneaux, D

    1986-06-01

    As interactions between peripheral chemoreceptors stimulation (PCS) and pulmonary vasomotor tone remain controversial, experiments were made in rats in order to clear up the effects of PCS on pulmonary arterial pressure (PAP). Different stimulations varying in intensities were used, in rats nervously intact (IR-rats), after vagotomy (XT-rats), after chemodenervation obtained without vagotomy (CDN not XT-rats) or with XT (CDN + XT) and finally after alpha 1-receptors blockade (P-rats = pretreated rats). The observed variations were analysed in view of disentangling reflex part of PCS from a direct activity on the pulmonary vascular bed. Ventilation, PAP and systemic blood pressure (BP) were studied in anaesthetized rats. N2 test, NaCN test, 20 s of 5% O2 inhalation and almitrine bismesylate (ALM) were used as PCS, ranged in the order of their relative intensities, from the ventilatory responses observed in IR-rats. In IR-rats, N2-and CN test produced a similar transient increase of PAP, slightly more extended than the hyperventilation. After XT, the responses were prolonged, but amplified only in CN test. Ventilatory responses disappear after CDN, but as far as pulmonary hypertension is concerned, CDN + XT is more potent than CDN without XT to reduce or even suppress them. This fact is particularly evident with ALM who is the strongest PCS used. Similar reduction of PAP rise was also produced in P-rats in which ventilatory responses remain unchanged. Prolonged hypoxic inhalation induced a progressive fall of systolic BP and of PAP. The return to normal air breathing is followed by BP restoration and a long-lasting PAP increase.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Differential changes in vascular mRNA levels between rat iliac and renal arteries produced by cessation of voluntary running.

    PubMed

    Padilla, Jaume; Jenkins, Nathan T; Roberts, Michael D; Arce-Esquivel, Arturo A; Martin, Jeffrey S; Laughlin, M Harold; Booth, Frank W

    2013-01-01

    Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel-lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short-term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days (n = 9; wheel-lock 7 day rats) or remained active in a second group for an additional 7 days (n = 9; wheel-lock 0 day rats). Real-time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro-atherogenic and anti-atherogenic genes. Compared with the iliac arteries of wheel-lock 0 day rats, iliac arteries of wheel-lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX-1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel-lock 0 day rats, renal arteries of wheel-lock 7 day rats exhibited decreased expression of ETb (-23%), p47phox (-32%) and p67phox (-19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short-term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries.

  12. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

    PubMed Central

    Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua

    2016-01-01

    Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980

  13. Involvement of interleukin-1 receptor mechanisms in development of arterial hypotension in rat heatstroke.

    PubMed

    Lin, M T; Liu, H H; Yang, Y L

    1997-10-01

    Rats, under urethan anesthesia, were exposed to a high ambient temperature (42 degrees C) to induce heatstroke and to assess the hemodynamic changes associated with heatstroke. Compared with normothermic controls, rats with heatstroke showed higher values of colonic temperature, heart rate, and plasma levels of interleukin (IL)-1 but lower values of R wave amplitude, P-R and Q-T intervals, systolic wave amplitude, diastolic and dicrotic wave duration, mean arterial pressure, stroke volume, and cardiac output. Animals injected intravenously with an IL-1-receptor antagonist at the time of heatstroke induction were protected from some of the cardiovascular effects of heatstroke, such as depressed ventricular depolarization, decreased stroke volume, decreased cardiac output, and arterial hypotension. The hemodynamic changes associated with heatstroke could be mimicked by IL-1beta administration. Other cardiovascular parameters such as total peripheral vascular resistance were unaffected by heatstroke induction or IL-1beta treatment. The results indicate that a selective decline in stroke volume or ventricular depolarization resulting from increased plasma levels of IL-1 may be an important mechanism signaling arterial hypotension or circulatory failure in rat heatstroke.

  14. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats.

    PubMed

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang; Fu, Enqing

    2015-06-01

    Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  15. Tenascin-C induces prolonged constriction of cerebral arteries in rats.

    PubMed

    Fujimoto, Masashi; Suzuki, Hidenori; Shiba, Masato; Shimojo, Naoshi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Kanamaru, Kenji; Matsushima, Satoshi; Taki, Waro

    2013-07-01

    Tenascin-C (TNC), a matricellular protein, is induced in association with cerebral vasospasm after subarachnoid hemorrhage. The aim of this study was to assess the vasoconstrictive effects of TNC and its mechanisms of action on cerebral arteries in vivo. Two dosages (1 and 10μg) of TNC were administered intracisternally to healthy rats, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72h after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24h. The effects of toll-like receptor 4 (TLR4) antagonists (LPS-RS), c-Jun N-terminal kinase (JNK), and p38 inhibitors (SP600125 and SB203580) on TNC-induced vasoconstriction were evaluated at 24h. Higher dosages of TNC induced more severe cerebral arterial constriction, which continued for more than 72h. TNC administration also upregulated TLR4, and activated JNK and p38 in the smooth muscle cell layer of the constricted cerebral artery. LPS-RS blocked TNC-induced TLR4 upregulation, JNK and p38 activation, and vasoconstrictive effects. SP600125 and SB203580 abolished TNC-induced TLR4 upregulation and vasoconstrictive effects. TNC may cause prolonged cerebral arterial constriction via TLR4 and activation of JNK and p38, which may upregulate TLR4. These findings suggest that TNC causes cerebral vasospasm and provides a novel therapeutic approach against it.

  16. TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats.

    PubMed

    Murphy, Timothy V; Kanagarajah, Arjna; Toemoe, Sianne; Bertrand, Paul P; Grayson, T Hilton; Britton, Fiona C; Leader, Leo; Senadheera, Sevvandi; Sandow, Shaun L

    2016-08-01

    This study investigated the expression and function of transient receptor potential vanilloid type-3 ion channels (TRPV3) in uterine radial arteries isolated from non-pregnant and twenty-day pregnant rats. Immunohistochemistry (IHC) suggested TRPV3 is primarily localized to the smooth muscle in arteries from both non-pregnant and pregnant rats. IHC using C' targeted antibody, and qPCR of TRPV3 mRNA, suggested pregnancy increased arterial TRPV3 expression. The TRPV3 activator carvacrol caused endothelium-independent dilation of phenylephrine-constricted radial arteries, with no difference between vessels from non-pregnant and pregnant animals. Carvacrol-induced dilation was reduced by the TRPV3-blockers isopentenyl pyrophosphate and ruthenium red, but not by the TRPA1 or TRPV4 inhibitors HC-030031 or HC-067047, respectively. In radial arteries from non-pregnant rats only, inhibition of NOS and sGC, or PKG, enhanced carvacrol-mediated vasodilation. Carvacrol-induced dilation of arteries from both non-pregnant and pregnant rats was prevented by the IKCa blocker TRAM-34. TRPV3 caused an endothelium-independent, IKCa-mediated dilation of the uterine radial artery. NO-PKG-mediated modulation of TRPV3 activity is lost in pregnancy, but this did not alter the response to carvacrol.

  17. Chromogranin A-derived peptides: interaction with the rat posterior cerebral artery.

    PubMed

    Mandalà, Maurizio; Brekke, Johan Fredrik; Serck-Hanssen, Guldborg; Metz-Boutigue, Marie-Hélène; Helle, Karen B

    2005-01-15

    Chromogranin A (CgA), an acidic granule protein of the regulated secretory pathway in the diffuse neuroendocrine system, is postulated to serve as a prohormone for regulatory peptides. Betagranin (rCgA(1-128)), the first N-terminal cleavage product of rat CgA, is 87% homologous to the bovine vasostatin I (bCgA(1-76)), previously shown to be vasoinhibitory in bovine resistance arteries. In this study the vasoactivity of homologous rat and bovine peptides was investigated in the rat posterior cerebral artery. Firstly, we examined the interaction of rhodamine (Rh)-labelled bCgA(7-40) and bCgA(47-70) with elements of the arterial wall by fluorescence microscopy. Secondly, rCgA(7-57), bCgA(1-40), bCgA(7-40) and bCgA(47-66) (chromofungin) were studied for effects on arterial tone and intracellular calcium as function of pressure in an arteriograph. Although without dilator or constrictor responses at 60-150 mm Hg, the rat peptide (rCgA(7-57)) evoked a significant delay in the onset of forced dilatation at 170 mm Hg, in contrast to the bovine peptides bCgA(1-40), bCgA(7-40) and bCgA(47-66) (chromofungin). Neither Rh-bCgA(7-40) nor Rh-bCgA(47-70) stained the endothelial layer, while Rh-bCgA(47-70) but not Rh-bCgA(7-40) stained the smooth muscle compartment. Analogously, bCgA(47-66) but not bCgA(7-40) reduced intracellular calcium, however without modifying the myogenic response. Thus, the betagranin peptide rCgA(7-57) and the two bovine chromofungin-containing peptides, highly homologous to the corresponding sequence (rCgA(47-66)), affected the rat cerebral artery without vasodilator effects, indicating significant species differences in vasoactivity of the N-terminal domain of CgA.

  18. Chemical sympathectomy induces arterial accumulation of native and oxidized LDL in hypercholesterolemic rats.

    PubMed

    Hachani, Rafik; Dab, Houcine; Sakly, Mohsen; Vicaut, Eric; Callebert, Jacques; Sercombe, Richard; Kacem, Kamel

    2012-01-26

    The aim of the present study was to examine the effect of sympathectomy on plasmatic and arterial native and oxLDL levels, as well as arterial LDL receptors (LDLR) and scavenger receptors in hypercholesterolemic rats, which are normally protected against atherosclerosis. Neonatal Wistar rats received subcutaneous injections of either guanethidine for sympathectomy (Gua+HC) or vehicle (HC), then were fed 1% cholesterol for three months. Intact normocholesterolemic rats were used as control of the HC group. Total cholesterol (TC) and LDL-cholesterol were evaluated in the plasma and the abdominal aorta by an auto-analyzer. Plasmatic and aortic oxLDL and native LDL-apo B100 were assessed by a sandwich ELISA. Aortic and hepatic native LDLR and aortic scavenger receptors (CD36 and SR-A) were quantified at mRNA and protein levels by real time PCR and western immunoblot. The effect of hypercholesterolemia was limited to an increase in plasmatic TC and LDL-cholesterol and a decrease in aortic apoB100 and aortic and hepatic LDLR. Hypercholesterolemia and sympathectomy in combination increased markedly plasmatic and aortic TC, LDL-cholesterol, apo B100 and oxLDL together with aortic scavenger receptors, but reduced markedly aortic and hepatic LDLR. Sympathectomy broke down the rat's protection against hypercholesterolemia by promoting accumulation of native and oxLDL in the aorta via scavenger receptors.

  19. Analysis of relaxation and repolarization mechanisms of nicorandil in rat mesenteric artery.

    PubMed Central

    Fujiwara, T.; Angus, J. A.

    1996-01-01

    1. The mechanisms by which nicorandil causes relaxation of rat isolated small mesenteric arteries mounted on a Mulvany myograph was investigated by use of a combination of putatively mechanism-specific antagonists. 2. In arteries precontracted by the thromboxane-mimetic, U46619, the EC50 for cromakalim and levcromakalim-induced relaxation curves were raised by 36 and 17 fold by glibenclamide (3 microM) while the EC50 for nicorandil-induced relaxation was unaffected by either glibenclamide or methylene blue (10 microM). A combination of these antagonists raised the EC50 for nicorandil by 8 fold. 3. In U46619-contracted arteries, nifedipine (100 nM) did not affect the cromakalim relaxation curve but it raised the EC50 for nicorandil by 5 fold. The combination of methylene blue, glibenclamide and nifedipine further inhibited the maximum relaxation to nicorandil. 4. In separate experiments, membrane potential (Em) and force responses were measured simultaneously. In arteries depolarized and contracted by U46619 both nicorandil and cromakalim repolarized (delta Em, 35 mV) and relaxed (100%) the vessels. Glibenclamide (3 microM) did not alter the relaxation-concentration curve to nicorandil but reduced the maximum repolarization to delta 10.8 mV. In contrast to Em and relaxation-response curves to cromakalim were shifted to the right by glibenclamide by 30-100 fold. 5. In unstimulated arteries, nicorandil (but not cromakalim) -induced hyperpolarization was significantly antagonized by methylene blue (10 microM) (6.6 fold rightward shift) or nifedipine (100 nM) (2.6 fold). In depolarized arteries (U46619), nifedipine but not methylene blue inhibited the nicorandil-induced hyperpolarization. 6. In arteries precontracted to 50% tissue maximum by either KCl or U46619, nifedipine (100 nM) relaxed the artery but failed to repolarize the Em. Presumably voltage-operated calcium channels (VOCC) were blocked preventing contraction but the artery remained depolarized, presumably

  20. Comparison of surgical methods of transient middle cerebral artery occlusion between rats and mice.

    PubMed

    Lee, Seunghoon; Hong, Yunkyung; Park, Sookyoung; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

    2014-12-01

    Rodent models of focal cerebral ischemia that do not require craniotomy have been developed by intraluminal suture middle cerebral artery occlusion (MCAo). Mouse MCAo models have been widely used and extended to genetic studies of cell death or recovery mechanisms. Therefore, we compared surgery-related parameters and techniques between such rats and mice. In rodent MCAo models, has to be considered body temperature during the operative period, as well as the need for the use of a standardized tip in terms of the outer diameter of probes. Induction of focal cerebral ischemia was measured by neurological dysfunction parameters. Our methods could induce stable moderate-severity ischemic brain injury models and histological alteration at 24 hr after MCAo surgery. Moreover approximately 80% (rats) and 85% (mice) survival ratios were shown indicating with model engineering success. Finally, we described and compared major parameters between rats and mice, including probe size, thread insert length, operation and occlusion periods, and differences in the procedures.

  1. Exercise restores beta-adrenergic vasorelaxation in aged rat carotid arteries.

    PubMed

    Leosco, Dario; Iaccarino, Guido; Cipolletta, Ersilia; De Santis, Domenico; Pisani, Eliana; Trimarco, Valentina; Ferrara, Nicola; Abete, Pasquale; Sorriento, Daniela; Rengo, Franco; Trimarco, Bruno

    2003-07-01

    Aging is associated with alterations in beta-adrenergic receptor (beta-AR) signaling and reduction in cardiovascular responses to beta-AR stimulation. Because exercise can attenuate age-related impairment in myocardial beta-AR signaling and function, we tested whether training could also exert favorable effects on vascular beta-AR responses. We evaluated common carotid artery responsiveness in isolated vessel ring preparations from 8 aged male Wistar-Kyoto (WKY) rats trained for 6 wk in a 5 days/wk swimming protocol, 10 untrained age-matched rats, and 10 young WKY rats. Vessels were preconstricted with phenylephrine (10-6 M), and vasodilation was assessed in response to the beta-AR agonist isoproterenol (10-10-3 x 10-8 M), the alpha2-AR agonist UK-14304 (10-9-10-6 M), the muscarinic receptor agonist ACh (10-9-10-6 M), and nitroprusside (10-8-10-5 M). beta-AR density and cytoplasmic beta-AR kinase (beta-ARK) activity were tested on pooled carotid arteries. beta-ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. beta-AR, alpha2-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored beta-AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced beta-AR number and increased beta-ARK activity. Training counterbalanced these phenomena and restored beta-AR density and beta-ARK activity to levels observed in young rat carotids. Our data indicate that age impairs beta-AR vasorelaxation in rat carotid arteries through beta-AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in beta-ARs and beta-ARK. Our data support an important role for beta-ARK in vascular beta-AR vasorelaxation.

  2. Insulin resistance in penile arteries from a rat model of metabolic syndrome

    PubMed Central

    Contreras, Cristina; Sánchez, Ana; Martínez, Pilar; Raposo, Rafaela; Climent, Belén; García-Sacristán, Albino; Benedito, Sara; Prieto, Dolores

    2010-01-01

    BACKGROUND AND PURPOSE Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vascular effects of insulin in penile arteries and whether these effects are impaired in a rat model of insulin resistance and metabolic syndrome. EXPERIMENTAL APPROACH Penile arteries from obese Zucker rats (OZR) and their counterpart, lean Zucker rats (LZR), were mounted on microvascular myographs and the effects of insulin were assessed in the absence and presence of endothelium and of specific inhibitors of nitric oxide (NO) synthesis, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). Insulin-induced changes in intracellular Ca2+ concentration [Ca2+]i were also examined. KEY RESULTS OZR exhibited mild hyperglycaemia, hypercholesterolemia, hypertryglyceridemia and hyperinsulinemia. Insulin induced endothelium- and NO-dependent relaxations in LZR that were impaired in OZR. Inhibition of PI3K reduced relaxation induced by insulin and by the β-adrenoceptor agonist isoprenaline, mainly in arteries from LZR. Antagonism of endothelin 1 (ET-1) receptors did not alter insulin-induced relaxation in either LZR or OZR, but MAPK blockade increased the responses in OZR. Insulin decreased [Ca2+]i, a response impaired in OZR. CONCLUSIONS AND IMPLICATIONS Insulin-induced relaxation was impaired in penile arteries of OZR due to altered NO release through the PI3K pathway and unmasking of a MAPK-mediated vasoconstriction. This vascular insulin resistance is likely to contribute to the endothelial dysfunction and erectile dysfunction associated with insulin resistant states. PMID:20735420

  3. Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

    PubMed Central

    Chen, Yulong; Zhang, Hongmei; Liu, Huanhuan; Cao, Ailan

    2016-01-01

    Independent of its lipid-lowering properties, simvastatin (Sim) induces vasorelaxation; however, the underlying mechanisms have remained elusive. The aim of the present study was to investigate the vasorelaxant effects of Sim on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro on a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (Emax)=51.05±4.09%; negative logarithm of the concentration that caused 50% of the maximum response (pD2)=4.17±0.18] or KCl (Emax=41.65±1.32%; pD2=3.55±0.1). Nω-nitro-L-arginine methyl ester (100 µM) significantly inhibited this effect, while it was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µM) and indomethacin (5 µM). In artery rings without endothelium, vasorelaxation induced by Sim was attenuated by 4-aminopyridine (100 µM), but was not affected by barium chloride dehydrate (10 µM), glibenclamide (10 µM) and traethylammonium chloride (1 mM). Moreover, Sim also inhibited the contraction induced by increasing external calcium in Ca2+-free medium with added KCl (60 mM). These results suggested that Sim induces relaxation of superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release and also through an endothelium-independent pathway, involving the opening of voltage-dependent K+ channels and blockade of extracellular Ca2+ influx.

  4. Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

    PubMed Central

    Chen, Yulong; Zhang, Hongmei; Liu, Huanhuan; Cao, Ailan

    2016-01-01

    Independent of its lipid-lowering properties, simvastatin (Sim) induces vasorelaxation; however, the underlying mechanisms have remained elusive. The aim of the present study was to investigate the vasorelaxant effects of Sim on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro on a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (Emax)=51.05±4.09%; negative logarithm of the concentration that caused 50% of the maximum response (pD2)=4.17±0.18] or KCl (Emax=41.65±1.32%; pD2=3.55±0.1). Nω-nitro-L-arginine methyl ester (100 µM) significantly inhibited this effect, while it was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µM) and indomethacin (5 µM). In artery rings without endothelium, vasorelaxation induced by Sim was attenuated by 4-aminopyridine (100 µM), but was not affected by barium chloride dehydrate (10 µM), glibenclamide (10 µM) and traethylammonium chloride (1 mM). Moreover, Sim also inhibited the contraction induced by increasing external calcium in Ca2+-free medium with added KCl (60 mM). These results suggested that Sim induces relaxation of superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release and also through an endothelium-independent pathway, involving the opening of voltage-dependent K+ channels and blockade of extracellular Ca2+ influx. PMID:27699019

  5. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats.

    PubMed

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB. PMID:27375765

  6. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats.

    PubMed

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB.

  7. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats

    PubMed Central

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P.; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB. PMID:27375765

  8. Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

    PubMed Central

    Caracuel, Laura; Callejo, María; Balfagón, Gloria

    2015-01-01

    Background and Purpose We investigated whether pregnancy was associated with changed function in components of perivascular mesenteric innervation and the mechanism/s involved. Experimental Approach We used superior mesenteric arteries from female Sprague-Dawley rats divided into two groups: control rats (in oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the vasoconstrictor response to electrical field stimulation (EFS) were analysed in the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release measured and neuronal NOS (nNOS) expression/activation analysed. Key Results EFS induced a lower frequency-dependent contraction in pregnant than in control rats. Phentolamine decreased EFS-induced vasoconstriction in segments from both experimental groups, but to a greater extent in control rats. EFS-induced vasoconstriction was increased by L-NAME in arteries from both experimental groups. This increase was greater in segments from pregnant rats. Pregnancy decreased NA release while increasing NO release. nNOS expression was not modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA-induced vasoconstriction response and did not modify DEA-NO-induced vasodilation response. Conclusions and Implications Neural control of mesenteric vasomotor tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic components both contributed to the decreased vasoconstriction response to EFS during pregnancy. All these changes indicate the selective participation of sympathetic and nitrergic innervations in vascular adaptations produced during pregnancy. PMID:25951331

  9. Alterations in Vasoreactivity of Femoral Artery Induced by Hindlimb Unweighting are Related to the Changes of Contractile Protein in Rats

    NASA Technical Reports Server (NTRS)

    Ma, Jin; Ren, Xinling; Meng, Qinjun; Zhang, Lifan; Purdy, Ralph E.

    2005-01-01

    Responses of endothelium removed femoral arterial rings to vasoactive compounds were examined in vitro, and the expression of Myosin and Actin of femoral artery were observed by Western Blotting and Immunohistochemistry in hndlimb unweighting rats and control rats. The results showed that contractile responses of femoral arterial rings evoked by Phenylephrine, Endothelin-1, Vasopressin, KCl, Ca(2+) and Ca(2+) ionophore A23187 were decreased in hindlimb unweighting rats as compared with that of controls. But vasoddatory responses induced by SNPand cGMP were not different between groups. No significant differences have been found in expressions of Calponin, Myosin, Actin, and the ratio of MHC SM1/SM2 between the two groups, but expression of alpha-SM-Actin decreased in hindlimb unweighting rats. The data indicated that the diminished contractile responsiveness probably result from altered contractile apparatus, especially the contractile proteins.

  10. Volume of myocardium perfused by coronary artery branches as estimated from 3D micro-CT images of rat hearts

    NASA Astrophysics Data System (ADS)

    Lund, Patricia E.; Naessens, Lauren C.; Seaman, Catherine A.; Reyes, Denise A.; Ritman, Erik L.

    2000-04-01

    Average myocardial perfusion is remarkably consistent throughout the heart wall under resting conditions and the velocity of blood flow is fairly reproducible from artery to artery. Based on these observations, and the fact that flow through an artery is the product of arterial cross-sectional area and blood flow velocity, we would expect the volume of myocardium perfused to be proportional to the cross-sectional area of the coronary artery perfusing that volume of myocardium. This relationship has been confirmed by others in pigs, dogs and humans. To test the body size-dependence of this relationship we used the hearts from rats, 3 through 25 weeks of age. The coronary arteries were infused with radiopaque microfil polymer and the hearts scanned in a micro- CT scanner. Using these 3D images we measured the volume of myocardium and the arterial cross-sectional area of the artery that perfused that volume of myocardium. The average constant of proportionality was found to be 0.15 +/- 0.08 cm3/mm2. Our data showed no statistically different estimates of the constant of proportionality in the rat hearts of different ages nor between the left and right coronary arteries. This constant is smaller than that observed in large animals and humans, but this difference is consistent with the body mass-dependence on metabolic rate.

  11. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    PubMed

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  12. Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats.

    PubMed

    Lee, Seung-Min; Moon, Jiyoung; Chung, Ji Hyung; Cha, Yong-Jun; Shin, Min-Jeong

    2013-07-01

    The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats. 24 male rats, 5 weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6 weeks. Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined. The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels. PT, aPTT and platelet aggregation were not significantly different among all tested groups. However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group. In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator. In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment. These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis.

  13. Arterial lesions and hypertension induced by saline, unilateral nephrectomy, and deoxycorticosterone in spontaneously hypertensive SHR rats.

    PubMed

    Wexler, B C

    1979-07-01

    Male and female, 100 days old, spontaneously hypertensive rats (SHR) were divided into two major groups: intact and uninephrectomized, given either no treatment, 1p.100 saline drinking water, 1p.100 saline + Deoxycorticosterone (DOC), or DOC alone. The DOC (Percorten pivalate) was given subcutaneously 2 times weekly, at a dose level of 2 mg/rat for 8 weeks. At autopsy, the combination of DOC + saline caused: the greatest exacerbation of blood pressure, marked catabolism, adrenal hypertrophy and thymic involution, little increase in heart weight, but a marked increase in kidney weight, elevated triglyceride and free fatty acids, cerebral and myocardial necrosis, fibrinous hyalinization of the cerebral, coronary, mesenteric, renal, testicular and ovarian arteries, foci of aortic cartilaginous metaplasia, PAN, foci of hepatic necrosis, and extensive lipid depletion from the zonae glomerulosa. Circulating corticosterone levels were suppressed to below normal levels. Excursion of circulating CPK levels coincided with the finding of myocardial necrosis and cerebral damage. It is suggested that the genetically-mediated hypertension of SHR is programmed through abnormal activity of the hypothalamic-pituitary axis and the specific morphologic make-up of arterial lesions is dependent upon the variety of adrenal or gonadal steroids secreted and their conditioning effect on the arterial wall.

  14. Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats.

    PubMed

    Lee, Seung-Min; Moon, Jiyoung; Chung, Ji Hyung; Cha, Yong-Jun; Shin, Min-Jeong

    2013-07-01

    The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats. 24 male rats, 5 weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6 weeks. Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined. The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels. PT, aPTT and platelet aggregation were not significantly different among all tested groups. However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group. In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator. In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment. These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis. PMID:23524316

  15. Measurement of chloride flux associated with the myogenic response in rat cerebral arteries.

    PubMed

    Doughty, J M; Langton, P D

    2001-08-01

    1. Self-referencing ion-selective (SERIS) electrodes were used to measure the temperature and pressure dependence of Cl(-) efflux, during myogenic contraction of pressurized rat cerebral resistance arteries. 2. At room temperature (18-21 degrees C), a small, pressure-independent Cl(-) efflux was measured. On warming to 37 degrees C, arteries developed pressure-dependent myogenic tone, and this was associated with a pressure-dependent increase in Cl(-) efflux (n = 5). 3. Both myogenic tone and the pressure- and temperature-dependent Cl(-) efflux were abolished on application of 10 microM tamoxifen, a Cl(-) channel blocker (IC(50) 3.75 +/- 0.2 microM). Tamoxifen (10 microM) also prevented contraction to 60 mM K(+), suggesting non-specific effects of tamoxifen (n = 5). 4. Myogenic tone was abolished by 2 microM nimodipine, but Cl(-) efflux was unaffected. In the presence of nimodipine, 10 microM tamoxifen still abolished pressure- and temperature-dependent Cl(-) efflux (n = 3). 5. In summary, a Cl(-) efflux can be measured from rat cerebral arteries, with a temperature dependence that is closely correlated with myogenic contraction. We conclude that Cl(-) efflux through Cl(-) channels contributes to the depolarization associated with myogenic contraction.

  16. Measurement of chloride flux associated with the myogenic response in rat cerebral arteries

    PubMed Central

    Doughty, Joanne M; Langton, Philip D

    2001-01-01

    Self-referencing ion-selective (SERIS) electrodes were used to measure the temperature and pressure dependence of Cl− efflux, during myogenic contraction of pressurized rat cerebral resistance arteries. At room temperature (18–21 °C), a small, pressure-independent Cl− efflux was measured. On warming to 37 °C, arteries developed pressure-dependent myogenic tone, and this was associated with a pressure-dependent increase in Cl− efflux (n = 5). Both myogenic tone and the pressure- and temperature-dependent Cl− efflux were abolished on application of 10 μm tamoxifen, a Cl− channel blocker (IC50 3.75 ± 0.2 μm). Tamoxifen (10 μm) also prevented contraction to 60 mm K+, suggesting non-specific effects of tamoxifen (n = 5). Myogenic tone was abolished by 2 μm nimodipine, but Cl− efflux was unaffected. In the presence of nimodipine, 10 μm tamoxifen still abolished pressure- and temperature-dependant Cl− efflux (n = 3). In summary, a Cl− efflux can be measured from rat cerebral arteries, with a temperature dependence that is closely correlated with myogenic contraction. We conclude that Cl− efflux through Cl− channels contributes to the depolarization associated with myogenic contraction. PMID:11483706

  17. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  18. Robustness of arterial blood gas analysis for assessment of respiratory safety pharmacology in rats.

    PubMed

    Whiteside, Garth T; Hummel, Michele; Boulet, Jamie; Beyenhof, Jessica D; Strenkowski, Bryan; John, Janet Dell; Knappenberger, Terri; Maselli, Harry; Koetzner, Lee

    2016-01-01

    Whole body plethysmography using unrestrained animals is a common technique for assessing the respiratory risk of new drugs in safety pharmacology studies in rats. However, wide variations in experimental technique make cross laboratory comparison of data difficult and raise concerns that non-appropriate conditions may mask the deleterious effects of test compounds - in particular with suspected respiratory depressants. Therefore, the objective of this study was to evaluate the robustness of arterial blood gas analysis as an alternative to plethysmography in rats. We sought to do this by assessing the effect of different vehicles and times post-surgical catheterization on blood gas measurements, in addition to determining sensitivity to multiple opioids. Furthermore, we determined intra-lab variability from multiple datasets utilizing morphine and generated within a single lab and lastly, inter-lab variability was measured by comparing datasets generated in two separate labs. Overall, our data show that arterial blood gas analysis is a measure that is both flexible in terms of experimental conditions and highly sensitive to respiratory depressants, two key limitations when using plethysmography. As such, our data strongly advocate the adoption of arterial blood gas analysis as an investigative approach to reliably examine the respiratory depressant effects of opioids. PMID:26589431

  19. Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation.

    PubMed

    Copp, Steven W; Stone, Audrey J; Li, Jianhua; Kaufman, Marc P

    2015-07-01

    IL-6 signaling via the soluble IL-6 receptor (sIL-6r) has been shown to increase primary afferent responsiveness to noxious stimuli. This finding prompted us to test the hypothesis that IL-6 and sIL-6r would increase the exercise pressor reflex in decerebrate rats with freely perfused femoral arteries. We also tested the hypothesis that soluble glycoprotein (sgp)130, an inhibitor of IL-6/sIL-6r signaling, would decrease the exaggerated exercise pressor reflex that is found in decerebrate rats with ligated femoral arteries. In rats with freely perfused femoral arteries, coinjection of 50 ng of IL-6 and sIL-6r into the arterial supply of the hindlimb significantly increased the peak pressor response to static (control: 14 ± 3 mmHg and IL-6/sIL-6r: 17 ± 2 mmHg, P = 0.03) and intermittent isometric (control: 10 ± 2 mmHg and IL-6/sIL-6r: 15 ± 4 mmHg, P = 0.03) hindlimb muscle contraction. In rats with ligated femoral arteries, injection of 50 ng of sgp130 into the arterial supply of the hindlimb reduced the peak pressor response to static (control: 24 ± 2 mmHg and sgp130: 16 ± 3 mmHg, P = 0.01) and intermittent isometric (control: 16 ± 2 mmHg and sgp130: 13 ± 2 mmHg, P = 0.04) hindlimb muscle contraction, whereas there was no effect of sgp130 on the exercise pressor reflex in rats with freely perfused femoral arteries. We conclude that coinjection of exogenous IL-6 and sIL-6r increased the exercise pressor reflex in rats with freely perfused femoral arteries. More importantly, we also conclude that IL-6 and sIL-6r play an endogenous role in evoking the exercise pressor reflex in rats with ligated femoral arteries but not in rats with freely perfused femoral arteries.

  20. Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation

    PubMed Central

    Stone, Audrey J.; Li, Jianhua; Kaufman, Marc P.

    2015-01-01

    IL-6 signaling via the soluble IL-6 receptor (sIL-6r) has been shown to increase primary afferent responsiveness to noxious stimuli. This finding prompted us to test the hypothesis that IL-6 and sIL-6r would increase the exercise pressor reflex in decerebrate rats with freely perfused femoral arteries. We also tested the hypothesis that soluble glycoprotein (sgp)130, an inhibitor of IL-6/sIL-6r signaling, would decrease the exaggerated exercise pressor reflex that is found in decerebrate rats with ligated femoral arteries. In rats with freely perfused femoral arteries, coinjection of 50 ng of IL-6 and sIL-6r into the arterial supply of the hindlimb significantly increased the peak pressor response to static (control: 14 ± 3 mmHg and IL-6/sIL-6r: 17 ± 2 mmHg, P = 0.03) and intermittent isometric (control: 10 ± 2 mmHg and IL-6/sIL-6r: 15 ± 4 mmHg, P = 0.03) hindlimb muscle contraction. In rats with ligated femoral arteries, injection of 50 ng of sgp130 into the arterial supply of the hindlimb reduced the peak pressor response to static (control: 24 ± 2 mmHg and sgp130: 16 ± 3 mmHg, P = 0.01) and intermittent isometric (control: 16 ± 2 mmHg and sgp130: 13 ± 2 mmHg, P = 0.04) hindlimb muscle contraction, whereas there was no effect of sgp130 on the exercise pressor reflex in rats with freely perfused femoral arteries. We conclude that coinjection of exogenous IL-6 and sIL-6r increased the exercise pressor reflex in rats with freely perfused femoral arteries. More importantly, we also conclude that IL-6 and sIL-6r play an endogenous role in evoking the exercise pressor reflex in rats with ligated femoral arteries but not in rats with freely perfused femoral arteries. PMID:25910806

  1. Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats.

    PubMed

    Wang, Zhongchao; Bai, Yungang; Yu, Jinwen; Liu, Huan; Cheng, Yaoping; Liu, Yonghong; Xie, Xiaoping; Ma, Jin; Bao, Junxiang

    2015-10-15

    Weightlessness induces the functional remodelling of arteries, but the changes to angiotensin II (Ang II)-elicited vasoconstriction and the underlying mechanism have never been reported. Caveolae are invaginations of the cell membrane crucial for the contraction of vascular smooth muscle cells, so we investigated the adaptation of Ang II-elicited vasoconstriction to simulated weightlessness and the role of caveolae in it. The 4 week hindlimb unweighted (HU) rat was used to simulate the effects of weightlessness. Ang II-elicited vasoconstriction was measured by isometric force recording. The morphology of caveolae was examined by transmission electron microscope. The binding of the angiotensin II type 1 receptor (AT1 ) and caveolin-1 (cav-1) was examined by coimmunoprecipitation and Western blot. We found that the maximal developing force (E(max)) of Ang II-elicited vasoconstriction was decreased in abdominal aorta by 30.6%, unchanged in thoracic aorta and increased in carotid artery by 17.9% after HU, while EC50 of the response was increased in all three arteries (P < 0.05). AT1 desensitization upon activation was significantly reduced by HU in all three arteries, as was the number of caveolae (P < 0.05). Furthermore, Ang II promoted the binding of AT1 and cav-1 significantly in control but not HU arteries. Both the number of caveolae and the binding of AT1 and cav-1 in HU arteries were restored by cholesterol pretreatment which also reinstated the change in EC50 as well as the level of AT1 desensitization. These results indicate that modified caveolae in vascular smooth muscle cells could interfere with the binding of AT1 and cav-1 mediating the adaptation of Ang II-elicited vasoconstriction to HU.

  2. High-fat diet increases O-GlcNAc levels in cerebral arteries: a link to vascular dysfunction associated with hyperlipidaemia/obesity?

    PubMed

    Lima, Victor V; Giachini, Fernanda R; Matsumoto, Takayuki; Li, Weiguo; Bressan, Alecsander F M; Chawla, Dhruv; Webb, R Clinton; Ergul, Adviye; Tostes, Rita C

    2016-06-01

    Obesity and high fat intake induce alterations in vascular function and structure. Aberrant O-GlcNAcylation (O-GlcNAc) of vascular proteins has been implicated in vascular dysfunction associated with cardiovascular and metabolic diseases. In the present study, we tested the hypothesis that high-fat diet (HFD)-mediated increases in O-GlcNAc-modified proteins contribute to cerebrovascular dysfunction. O-GlcNAc-protein content was increased in arteries from male Wistar rats treated with a HFD (45% fat) for 12 weeks compared with arteries from rats on control diet (CD). HFD augmented body weight [(g) 550±10 compared with 502±10 CD], increased plasma triacylglycerols [(mg/dl) 160±20 compared with 95±15 CD] and increased contractile responses of basilar arteries to serotonin [5-hydroxytryptamine (5-HT)] [(pD2) 7.0±0.1 compared with 6.7±0.09 CD] and the thromboxane analogue 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619) [(pD2) 7.2±0.1 compared with 6.8±0.09 CD]. Of importance, increased levels of O-GlcNAc [induced by 24 h-incubation of vessels with a potent inhibitor of O-GlcNAcase (OGA), O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PugNAc)] increased basilar artery contractions in response to U-46619 [(pD2) 7.4±0.07 compared with 6.8±0.08 CD] and 5-HT [(pD2) 7.5±0.06 compared with 7.1±0.1 CD]. Vessels from rats on the HFD for 12 weeks and vessels treated with PugNAc displayed increased phosphorylation of p38 (Thr(180/182)) and extracellular signal-regulated kinase 1/2 (Erk1/2) (Ser(180/221)). Increased 5HT-induced contractions in arteries from rats on the HFD or in arteries incubated with PugNAc were abrogated by mitogen-activated protein kinase (MAPK) inhibitors. Our data show that HFD augments cerebrovascular O-GlcNAc and this modification contributes to increased contractile responses and to the activation of the MAPK pathway in the rat basilar artery.

  3. Effect of diesel emissions and coal dust inhalation on heart and pulmonary arteries of rats

    SciTech Connect

    Vallyathan, V.; Virmani, R.; Rochlani, S.; Green, F.H.; Lewis, T.

    1986-01-01

    Fischer 344 (SPF) rats were exposed by inhalation to respirable particulate levels of 2 mg/m3 diesel emissions, diesel emissions plus coal dust, coal dust, or air for 7 h/d, 5 d/wk for 24 mo. The effects of treatment on body and heart weights, right and left ventricular wall thickness, severity of cardiomyopathy, and changes in the small pulmonary arteries were evaluated after 24 mo of exposure. In all dust-exposed animals, light microscopic examination of the lungs revealed dust-laden macrophages in alveolar spaces and focal accumulations of dust-laden macrophages near the respiratory bronchioles associated with hyperplasia of type II cells. This response was more prominent in animals exposed to diesel emissions alone. Age-related myocardial fibrosis and inflammatory infiltrates were common in all four groups. No statistically significant differences were detected between the groups for heart weights, ventricular wall thickness, and pulmonary arterial wall thickness. However, animals exposed to diesel emissions did show a consistent trend toward increased pulmonary arterial wall thickness, for all size categories of artery, compared to controls.

  4. Novel dual endothelin receptor antagonist macitentan reverses severe pulmonary arterial hypertension in rats.

    PubMed

    Kunita-Takanezawa, Mutsumi; Abe, Kohtaro; Hirooka, Yoshitaka; Kuwabara, Yukimitsu; Hirano, Katsuya; Oka, Masahiko; Sunagawa, Kenji

    2014-11-01

    The efficacy of endothelin (ET) receptor antagonist bosentan in patients with severe pulmonary arterial hypertension (PAH) remains limited, partly because its higher doses for potential blockade of ET receptors have never been tested due to liver dysfunction. We hypothesized that rigorous blockade of ET receptors using the novel dual ET receptor antagonist macitentan would be effective in treating severe PAH without major side effects in a preclinical model appropriately representing the human disorder. In normal rats, 30 mg·kg·d of macitentan completely abolished big ET-1-induced increases in right ventricle (RV) systolic pressure. Adult male rats were injected with SU5416, a vascular endothelial growth factor blocker, and exposed to hypoxia for 3 weeks and then to normoxia for an additional 5 weeks (total 8 weeks). In intrapulmonary arterial rings isolated from rats with severe PAH, macitentan concentration dependently inhibited ET-1-induced contraction. Long-term treatment with macitentan (30 mg·kg·d, from week 3 to 8) reversed the high RV systolic pressure with preserved cardiac output. Development of RV hypertrophy, luminal occlusive lesions and medial wall thickening were also significantly improved without increasing serum levels of liver enzymes by macitentan. In conclusion, efficacious blockade of ET receptors with macitentan would reverse severe PAH without major adverse effects.

  5. Transneuronal Degeneration of Thalamic Nuclei following Middle Cerebral Artery Occlusion in Rats

    PubMed Central

    2016-01-01

    Objective. Postinfarction transneuronal degeneration refers to secondary neuronal death that occurs within a few days to weeks following the disruption of input or output to synapsed neurons sustaining ischemic insults. The thalamus receives its blood supply from the posterior circulation; however, infarctions of the middle cerebral arterial may cause secondary transneuronal degeneration in the thalamus. In this study, we presented the areas of ischemia and associated transneuronal degeneration following MCAo in a rat model. Materials and Methods. Eighteen 12-week-old male Sprague-Dawley rats were randomly assigned to receive middle cerebral artery occlusion surgery for 1, 7, and 14 days. Cerebral atrophy was assessed by 2,3,5-triphenyltetrazolium hydrochloride staining. Postural reflex and open field tests were performed prior to animal sacrifice to assess the effects of occlusion on behavior. Results. Myelin loss was observed at the lesion site following ischemia. Gliosis was also observed in thalamic regions 14 days following occlusion. Differential degrees of increased vascular endothelial growth factor expression were observed at each stage of infarction. Increases in myelin basic protein levels were also observed in the 14-day group. Conclusion. The present rat model of ischemia provides evidence of transneuronal degeneration within the first 14 days of occlusion. The observed changes in protein expression may be associated with self-repair mechanisms in the damaged brain. PMID:27597962

  6. Transneuronal Degeneration of Thalamic Nuclei following Middle Cerebral Artery Occlusion in Rats.

    PubMed

    Chang, Shu-Jen; Cherng, Juin-Hong; Wang, Ding-Han; Yu, Shu-Ping; Liou, Nien-Hsien; Hsu, Ming-Lun

    2016-01-01

    Objective. Postinfarction transneuronal degeneration refers to secondary neuronal death that occurs within a few days to weeks following the disruption of input or output to synapsed neurons sustaining ischemic insults. The thalamus receives its blood supply from the posterior circulation; however, infarctions of the middle cerebral arterial may cause secondary transneuronal degeneration in the thalamus. In this study, we presented the areas of ischemia and associated transneuronal degeneration following MCAo in a rat model. Materials and Methods. Eighteen 12-week-old male Sprague-Dawley rats were randomly assigned to receive middle cerebral artery occlusion surgery for 1, 7, and 14 days. Cerebral atrophy was assessed by 2,3,5-triphenyltetrazolium hydrochloride staining. Postural reflex and open field tests were performed prior to animal sacrifice to assess the effects of occlusion on behavior. Results. Myelin loss was observed at the lesion site following ischemia. Gliosis was also observed in thalamic regions 14 days following occlusion. Differential degrees of increased vascular endothelial growth factor expression were observed at each stage of infarction. Increases in myelin basic protein levels were also observed in the 14-day group. Conclusion. The present rat model of ischemia provides evidence of transneuronal degeneration within the first 14 days of occlusion. The observed changes in protein expression may be associated with self-repair mechanisms in the damaged brain. PMID:27597962

  7. Potent vasoconstrictor actions of cyclopiazonic acid and thapsigargin on femoral arteries from spontaneously hypertensive rats

    PubMed Central

    Nomura, Yukiko; Asano, Masahisa; Ito, Katsuaki; Uyama, Yoshiaki; Imaizumi, Yuji; Watanabe, Minoru

    1996-01-01

    The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents which inhibit the Ca2+-ATPase of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY).In resting strips preloaded with fura-PE3, the addition of CPA (10 μM) or thapsigargin (100 nM) caused an elevation of cytosolic Ca2+ level ([Ca2+]i) and a contraction. These responses were significantly greater in SHR than in WKY.The addition of verapamil (3 μM) to the resting strips caused a decrease in resting [Ca2+]i, which was significantly greater in SHR than in WKY. In SHR, but not in WKY, this decrease was accompanied by a relaxation from the resting tone, suggesting the maintenance of myogenic tone in the SHR artery.Verapamil (3 μM) abolished differences between SHR and WKY. The effects of verapamil were much greater on the contraction than on the [Ca2+]i.The resting Ca2+ influx in arteries measured after a 5 min incubation of the artery with 45Ca was not increased by CPA or thapsigargin in either SHR or WKY. The net Ca2+ entry measured after a 30 min incubation of the artery with 45Ca was decreased by CPA or thapsigargin in both SHR and WKY. The resting Ca2+ influx was significantly higher in SHR than in WKY, and was decreased by nifedipine (100 nM) in the SHR artery, but was unchanged in the WKY artery.The resting 45Ca efflux from the artery was increased during the addition of CPA (10 μM). This increase was less in SHR than in WKY. The resting 45Ca efflux was the same in SHR and WKY.These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels (VDCCs) was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2

  8. Exercise training improves early survival rate in diabetic rats submitted to acute coronary artery ligation.

    PubMed

    Nadeau, A; Rousseau-Migneron, S; Tancrède, G

    1988-09-01

    This study was designed to test the hypothesis that the decreased early survival rate of diabetic rats submitted to acute experimental myocardial infarction could be improved by a previous training program. Male Wistar rats (+/- 200 g) were rendered diabetic with the i.v. injection of streptozotocin (45 mg/kg) but only those presenting one week later a tail-blood glucose value between 250-400 mg/dl were retained in the protocol. Diabetic and control rats were either kept sedentary or submitted to a progressive 10-week program of treadmill running. The left coronary artery was then ligated under ether anesthesia. Adequate occlusion was confirmed by an elevation of plasma CK-MB levels four hours later or by a toluidine blue injection technique in rats which died earlier. Since the first 20 minutes after such a procedure represents a most critical period for sudden death, the early survival rate was calculated for each group of rats and significance in differences was established with the Fisher's test. While the 27% early survival rate observed in sedentary diabetics was significantly lower (p = 0.02) than the 49% found in sedentary controls, this was completely alleviated by previous training in diabetic animals (50%; p = 0.018 vs sedentary diabetics and 0.623 vs sedentary controls). This beneficial effect of training was not found in nondiabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Rapid elongation of arteries and veins in rats with a tissue expander.

    PubMed

    Stark, G B; Hong, C; Futrell, J W

    1987-10-01

    The saphenous arteries and veins of 40 rats were elongated with 20-cc tissue expanders underlying the leg adductor muscles. The mean rate of successful elongation of the vessels was 84 +/- 47 percent SD, with a maximum gain of 140 percent. The fastest mean elongation velocity reached 45 percent per day. Thrombosis occurred only with stretching velocities of more than 10 percent per day, which seemed to be a safe margin. Distribution of the volume into many intervals was safer than infrequent high-volume injections. Histology showed no reduction in vessel wall diameter or loss intimal integrity. Subendothelial cellular proliferation was an indicator of this rapid regeneration. Microvascular anastomoses performed in elongated arteries and veins had the same patency rate (90 percent) as in controls.

  10. Alpha 1D- and alpha 1A-adrenoceptors mediate contraction in rat renal artery.

    PubMed

    Villalobos-Molina, R; López-Guerrero, J J; Ibarra, M

    1997-03-19

    To investigate the alpha 1-adrenoceptor subtype(s) mediating contraction in rat renal artery, we have compared the effect of the alpha 1-adrenoceptor antagonists, 5-methylurapidil, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl) 8-azaspiro (4.5) decane-7,9-dione 2HCl) and chloroethylclonidine on functional responses to noradrenaline. A clear blockade by chloroethylclonidine (10(-4) M) of noradrenaline-induced contraction was observed and, along with this effect. pKB values of 9.12 and 8.40 for BMY 7378 and 9.75 and 10.06 for 5-methylurapidil were obtained, indicating that the renal artery expresses the alpha 1D-adrenoceptor subtype as the one involved in contraction and not only the alpha 1A subtype as has been reported. PMID:9098691

  11. The Arteries of the Brain in Hare (Lepus europaeus Pallas, 1778).

    PubMed

    Brudnicki, Witold; Kirkiłło-Stacewicz, Krzysztof; Skoczylas, Benedykt; Nowicki, Włodzimierz; Jabłoński, Ryszard; Brudnicki, Adam; Wach, Jan

    2015-10-01

    Research into course and variability of brain arteries in hare were performed on 38 adult hares of both sexes (males 23 and females 15). The arteries were filled with a synthetic latex at a constant pressure introduced with a medical syringe to the left ventricle. The source of blood supply to the brain was internal carotid arteries, whose branches formed an arterial circle of the brain, vertebral arteries, and basilar artery as the result of its anastomosis. Variability focused on a method of departure of middle cerebral arteries, which were multiple vessels in 39.5% of cases and rostral cerebellar arteries. Caudal communicating arteries in hare comprised bilateral anastomosis of internal carotid arteries and final branches of the basilar artery. It stabilized the steady flow of blood to all parts of the brain. Caudal cerebral arteries comprised final branches of the basilar artery. The largest capacity of all the arteries of the brain was observed in the main trunk of the basilar artery. The capacity of these vessels was 4.53 mm(3) on average. The factor of capacity of cerebral arteries in relation to weight of the brain reaches a high value in hare.

  12. Vasorelaxant activities of Danhong injection and their differential effects on the rat abdominal aorta and mesenteric artery.

    PubMed

    Su, Xianming; Zhi, Xiaowen; Cui, Ting; Zheng, Qiaowei; Wang, Shixiang; Cao, Yongxiao; Cui, Changcong; Feng, Weiyi

    2015-01-01

    Previous studies have found that Danhong injection (DHI), an extensively used herbal extract preparation in China, might be a powerful vasodilator. The aims of this study were to determine the vascular activity of DHI and its effects on arteries of different sizes. The results showed that DHI significantly inhibited rat-hindquarters and rabbit-ear vasoconstriction elicited by norepinephrine (NE) perfusion and markedly relaxed KCl-contracted and NE-contracted rat abdominal aortic and mesenteric artery rings. The endothelium made only a minor contribution to the vasorelaxant effect of DHI on artery segments. The vasorelaxant effect of DHI varied with the artery size, with larger arteries exhibiting a more sensitive and potent vasodilator response. DHI relaxed NE-induced vasoconstriction probably through inhibition of the intracellular Ca2+ release through the inositol triphosphate receptor system in the abdominal aorta and mesenteric artery, along with blockage of extracellular Ca2+ influx through the receptor-linked Ca2+ channels in the mesenteric artery. In addition, DHI completely relaxed KCl-induced contraction in both of the arteries, suggesting that inhibition of Ca2+ influx through voltage-gated Ca2+ channels is involved in the vasorelaxant effect of DHI. This elucidation of the vascular effects of DHI and the underlying mechanisms could lead to improved clinical applications.

  13. Effect of tromethamine (THAM) on infarct volume following permanent middle cerebral artery occlusion in rats.

    PubMed

    Kiening, K L; Schneider, G H; Unterberg, A W; Lanksch, W R

    1997-01-01

    This study investigates the influence on tromethamine (THAM) on ischemic volume induced by permanent middle cerebral artery occlusion (MCAO) in rats. 14 male Sprague Dawley rats underwent left sided permanent MCAO by electro coagulation. Animals were treated either by 3-M THAM given intravenously in a single dosage of 0.6 mmol/kg body weight (THAM group: n = 7) 10 min following MCAO and again 1, 2, 3, 4 and 5 hours later or by NaCl 0.9% (placebo group: n = 7) in the same mode. Mean arterial blood pressure (MABP) was monitored for 30 min post MCAO and arterial blood gases were taken 10 min after the first injection. The extent of ischemia volume was assessed by planimetry of coronal sections stained with triphenyl-tetrazolium chloride (TTC) and with hematoxilin/eosin (HE). Tests for significance were accomplished by ANOVA on ranks. A difference of p < 0.05 was considered significant. The THAM group showed an insignificant decrease in MABP 1 min after injection (THAM: 75 +/- 11 mmHg, placebo: 86 +/- 10 mmHg). Arterial pH was significantly different (THAM: 7.46 +/- 0.04; placebo: 7.32 +/- 0.03). In TTC staining, the ischemia volume--given in absolute values and percentage of the total left volume--was significantly reduced in the THAM group (THAM: 43.9 +/- 8.3 mm3/7.0 +/- 1.3%; placebo: 95.2 +/- 13.8 mm3/14.2 +/- 2.0%). In HE staining, the reduction of ischemia, volume did not reach statistical significance (THAM: 49.1 +/- 9.9 mm3/9.6 +/- 1.8%; placebo: 66.3 +/- 14.5 mm3/13.1 +/- 2.8%). Based on these results, a moderate neuroprotective effect of THAM in experimental cerebral infarction could be demonstrated. PMID:9416318

  14. Hydrogen sulfide attenuates ferric chloride-induced arterial thrombosis in rats.

    PubMed

    Qin, Yi-Ren; You, Shou-Jiang; Zhang, Yan; Li, Qian; Wang, Xian-Hui; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

    2016-06-01

    Hydrogen sulfide (H2S) is a novel gaseous transmitter, regulating a multitude of biological processes in the cardiovascular and other systems. However, it remains unclear whether it exerts any effect on arterial thrombosis. In this study, we examined the effect of H2S on ferric chloride (FeCl3)-induced thrombosis in the rat common carotid artery (CCA). The results revealed a decrease of the H2S-producing enzyme cystathionine γ-lyase (CSE) expression and H2S production that persisted until 48 h after FeCl3 application. Intriguingly, administration with NaHS at appropriate regimen reduced the thrombus formation and enhanced the blood flow, accompanied with the alleviation of CSE and CD31 downregulation, and endothelial cell apoptosis in the rat CCA following FeCl3 application. Moreover, the antithrombotic effect of H2S was also observed in Rose Bengal photochemical model in which the development of thrombosis is contributed by oxidative injury to the endothelium. The in vitro study demonstrated that the mRNA and protein expression of CSE, as well as H2S production, was decreased in hydrogen peroxide (H2O2)-treated endothelial cells. Exogenous supplement of NaHS and CSE overexpression consistently alleviated the increase of cleaved caspase-3 and endothelial cell damage caused by H2O2. Taken together, our findings suggest that endogenous H2S generation in the endothelium may be impaired during arterial thrombosis and that modulation of H2S, either exogenous supplement or boost of endogenous production, may become a potential venue for arterial thrombosis therapy.

  15. Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors

    PubMed Central

    Geary, Greg G; Duckles, Sue P; Krause, Diana N

    1998-01-01

    The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat.Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and α1-adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation.The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium-denuded arteries. While melatonin does not appear to modulate agonist-induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress.When the Ca2+-activated K+ channel opener, NS 1619 (10 μM), was present, potentiating effects of melatonin were restored in endothelium-denuded vessels. However, addition of the opener of ATP-sensitive K+ channels, cromakalim (3 μM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+-activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+-activated K+ channels to produce its potentiating effects.Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+-activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow-induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone. PMID:9605558

  16. Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat.

    PubMed Central

    Garcia, J. H.; Yoshida, Y.; Chen, H.; Li, Y.; Zhang, Z. G.; Lian, J.; Chen, S.; Chopp, M.

    1993-01-01

    Focal brain ischemia induced in rats by occlusion of an intracranial artery is a widely used paradigm of human brain infarct. Details of the structural changes that develop in either the human or the rat brain at various times after occlusion of an intracranial artery are incompletely characterized. We studied, in 48 adult Wistar rats, structural alterations involving the cerebral hemisphere ipsilateral to an arterial occlusion, at intervals ranging from 30 min to 7 days. Microscopic changes developed over time in separate areas of the corresponding cerebral hemisphere in a predictable pattern, appearing as small lesions in the preoptic area (30 minutes), enlarging to involve the striatum, and finally involving the cerebral cortex. Two types of neuronal responses were noted according to the time elapsed; acute changes (up to 6 hours) included scalloping, shrinkage, and swelling, whereas delayed changes (eosinophilia and karyolysis) appeared later (> or = 12 hours). Three types of astrocytic responses were noted. 1) Cytoplasmic disintegration occurred in the preoptic area at a time and in a place where neurons appeared minimally injured. 2) Nuclear and cytoplasmic swelling were prominent responses in the caudoputamen and cerebral cortex at a time when neurons showed minimal alterations. 3) Increased astrocytic glial fibrillary acidic protein reactivity was noted at the interface between the lesion and the surrounding brain tissue after 4 to 6 hours. The gross pattern of the brain lesion and the maturation of neuronal changes typical of a brain infarct have a predictable progression. Focal brain ischemia of up to 6-hour duration does not induce coagulation necrosis. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8434652

  17. Effects of tyrosine kinase inhibitors on the contractility of rat mesenteric resistance arteries.

    PubMed Central

    Toma, C; Jensen, P E; Prieto, D; Hughes, A; Mulvany, M J; Aalkjaer, C

    1995-01-01

    1. A pharmacological characterization of tyrosine kinase inhibitors (TKI) belonging to two distinct groups (competitors at the ATP-binding site and the substrate-binding site, respectively) was performed, based on their effects on the contractility of rat mesenteric arteries. 2. Both the ATP-site competitors (genistein and its inactive analogue, daidzein) and the substrate-site competitors (tyrphostins A-23, A-47 and the inactive analogue, A-1) reversibly inhibited noradrenaline (NA, (10 microM)) and KCl (125 mM) induced contractions, concentration-dependently. Genistein was slightly but significantly more potent than daidzein; the tyrphostins were all less potent than genistein, and there were no significant differences between the individual potencies. The tyrosine kinase substrate-site inhibitor bis-tyrphostin had no inhibitory effect. 3. Genistein, daidzein, A-23 and A-47 each suppressed the contraction induced by Ca2+ (1 microM) in alpha-toxin permeabilized arteries. A-1 and bis-tyrphostin had little or no effect on contraction of the permeabilized arteries. 4. Genistein was significantly more potent than daidzein with respect to inhibition of the contraction induced by 200 nM Ca2+ in the presence of NA (100 microM) and GTP (3 microM). The effect of A-23, A-47, A-1 and bis-tyrphostin was similar in permeabilized arteries activated with Ca2+ (200 nM) + NA (100 microM) + GTP (3 microM) and permeabilized arteries activated with 1 microM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7620718

  18. Recovery from carotid artery catheterization performed under various anesthetics in male, Sprague-Dawley rats.

    PubMed

    Lawson, D M; Duke, J L; Zammit, T G; Collins, H L; DiCarlo, S E

    2001-07-01

    This study was designed to determine the time to recovery from carotid artery catheterization using multiple criteria and to compare recovery times between three common anesthetics. Male Sprague-Dawley rats, chronically instrumented with radio-telemetry transmitters, were anesthetized with sodium pentobarbital, halothane or a mixture of ketamine, xylazine and acepromazine before an indwelling catheter was placed in the carotid artery. The procedure was completed in less than 15 min. Changes in body weight, food and water consumption, blood pressure, heart rate and activity were used to determine recovery. As judged by recovery of body weight, animals anesthetized with each of the anesthetics recovered by the 4th day after catheterization. Food and water consumption normalized by 1-2 days after surgery. Heart rates and blood pressures during the light phase of the photoperiod were significantly increased for 2 days by all anesthetics. During the dark phase of the photoperiod, heart rates and blood pressures were not significantly affected by pentobarbital or halothane anesthesia, but were significantly decreased and increased respectively on the night immediately following surgery in the ketamine / xylazine / acepromazine-anesthetized rats. Delayed elevations of heart rate were observed in pentobarbital and halothane anesthetized rats on days and/or nights 5 and 6 post surgery. Animal activity patterns during the light phase of the photoperiod were not affected by pentobarbital or halothane, but were increased by ketamine 2 days after surgery. During the dark phase, halothane transiently reduced activity whereas ketamine-anesthetized rats showed reduced activity for 4 nights post surgery. These studies show that recovery depends on the criteria selected and the anesthetic used, but, in general, 2-4 days were required for recovery from this relatively simple procedure.

  19. Effects of skeletal unloading on the vasomotor properties of the rat femur principal nutrient artery

    PubMed Central

    Prisby, Rhonda D.; Behnke, Bradley J.; Allen, Matthew R.

    2015-01-01

    Spaceflight and prolonged bed rest induce deconditioning of the cardiovascular system and bone loss. Previous research has shown declines in femoral bone and marrow perfusion during unloading and with subsequent reloading in hindlimb-unloaded (HU) rats, an animal model of chronic disuse. We hypothesized that the attenuated bone and marrow perfusion may result from altered vasomotor properties of the bone resistance vasculature. Therefore, the purpose of this study was to determine the effects of unloading on the vasoconstrictor and vasodilator properties of the femoral principal nutrient artery (PNA), the main conduit for blood flow to the femur, in 2 wk HU and control (CON) rats. Vasoconstriction of the femoral PNA was assessed in vitro using norepinephrine, phenylephrine, clonidine, KCl, endothelin-1, arginine vasopressin, and myogenic responsiveness. Vasodilation through endothelium-dependent [acetylcholine, bradykinin, and flow-mediated dilation (FMD)] and endothelium-independent mechanisms [sodium nitroprusside (SNP) and adenosine] were also determined. Vasoconstrictor responsiveness of the PNA from HU rats was not enhanced through any of the mechanisms tested. Endothelium-dependent vasodilation to acetylcholine (CON, 86 ± 3%; HU, 48 ± 7% vasodilation) and FMD (CON, 61 ± 9%; HU, 11 ± 11% vasodilation) were attenuated in PNAs from HU rats, while responses to bradykinin were not different between groups. Endothelium-independent vasodilation to SNP and adenosine were not different between groups. These data indicate that unloading-induced decrements in bone and marrow perfusion and increases in vascular resistance are not the result of enhanced vasoconstrictor responsiveness of the bone resistance arteries but are associated with reductions in endothelium-dependent vasodilation. PMID:25635000

  20. Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

    PubMed

    Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

    2014-02-01

    Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

  1. Influence of regular exercise on age-related changes in arterial elasticity: mechanistic insights from wall compositions in rat aorta.

    PubMed

    Nosaka, Toshiya; Tanaka, Hirofumi; Watanabe, Izumi; Sato, Masaaki; Matsuda, Mitsuo

    2003-04-01

    Arterial stiffness increases with age in healthy sedentary adults. We previously reported that the age-related increases in arterial stiffness are absent or attenuated in regularly exercising adults. However, the mechanism underlying this training effect is unknown. One possibility is that regular exercise minimizes age-related changes in the arterial wall composition of elastin and collagen. To gain insight into this issue, we studied four groups of rats (N = 23): young (42-46 wks) and old (80-84 wks), sedentary and exercise-trained. The exercise group swam 1 hr.d-1, 6 d.wk-1 for 17-21 weeks. There was no significant difference in the incremental elastic modulus between young sedentary and exercise-trained rats. The elastic moduli of the old exercise-trained rats were 31% lower than in the old sedentary controls. As such, the magnitude of age-related increase in the elastic modulus was smaller in the exercise-trained (110%) vs. the sedentary group (151%) (p < 0.05). In both activity groups, elastin content was lower and collagen content was higher in old vs. young rats (p < 0.05). However, there were no significant differences between the two activity groups. These results are not consistent with the hypothesis that regular physical exercise minimizes age-related compositional changes in the arterial wall and attenuates the age-related increase in arterial stiffness.

  2. Effects of middle cerebral artery occlusion on baroreceptor reflex control of heart rate in the rat.

    PubMed

    Saad, M A; Huerta, F; Trancard, J; Elghozi, J L

    1989-07-01

    Neurons in the insular cortex have recently been shown to innervate medullary autonomic nuclei such as the nucleus tractus solitarii (NTS). The present study examines the effect of lesioning the insular cortex on baroreceptor-heart rate reflex in conscious rats. We did this by occluding the stem of the left proximal middle cerebral artery which causes a lesion of the insular and adjacent lateral frontoparietal cortices. Nine and 10 days after lesioning or sham operation, reflex heart rate responses were recorded following i.v. doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by computerized sigmoidal curve-fitting. The overall contribution of the sympathetic and the cardiac vagus were assessed by using peripherally acting muscarinic and beta-adrenoceptor antagonists, respectively. Lesioned rats were compared to sham-operated rats. Lesioning the insular cortex did not affect mean blood pressure and heart rate. However, the lesion selectively enhanced reflex vagal bradycardia that occurred when mean blood pressure was artificially elevated. A greater vagal bradycardia with no change in the upper plateau indicated that ischemia was acting entirely on the baroreflex-dependent vagal cardiac motoneurons. There was no effect on the sympathetic heart rate range but the normalized gain of the sympathetic component was increased in those lesioned rats. These observations suggest that the unilateral cortical lesion chronically affected the baroreceptor control of heart rate through mechanisms differentially affecting the vagus and the cardiac sympathetic nerves. PMID:2778268

  3. Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

    NASA Technical Reports Server (NTRS)

    Nyhan, Daniel; Kim, Soonyul; Dunbar, Stacey; Li, Dechun; Shoukas, Artin; Berkowitz, Dan E.

    2002-01-01

    Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

  4. Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

    PubMed Central

    Veitenheimer, Britta

    2013-01-01

    Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ∼15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension. PMID:23161878

  5. Endoperoxide 4 receptors play a role in evoking the exercise pressor reflex in rats with simulated peripheral artery disease

    PubMed Central

    Yamauchi, Katsuya; Kim, Joyce S; Stone, Audrey J; Ruiz-Velasco, Victor; Kaufman, Marc P

    2013-01-01

    Ligating the femoral artery for 72 h in decerebrated rats exaggerates the exercise pressor reflex. The sensory arm of this reflex is comprised of group III and IV afferents, which can be either sensitized or stimulated by PGE2. In vitro studies showed that endoperoxide (EP) 3 and 4 receptors were responsible for the PGE2-induced sensitization of rat dorsal root ganglion cells. This in vitro finding prompted us to test the hypothesis that blockade of EP3 and/or EP4 receptors attenuated the exaggerated exercise pressor reflex in rats with ligated femoral arteries. We measured the cardiovascular responses to static hindlimb contraction or tendon stretch before and after femoral arterial injection of L798106 (an EP3 antagonist) or L161982 (an EP4 antagonist). The pressor and cardioaccelerator responses to either contraction or tendon stretch were not attenuated by L798106 in either the ligated or freely perfused rats. Likewise in five rats whose hindlimb muscles were freely perfused, the pressor and cardioaccelerator responses to either contraction or tendon stretch were not attenuated by L161982. In the six ligated rats, however, the pressor response to contraction was attenuated by L161982, averaging 37 ± 3 mmHg before, 18 ± 2 mmHg afterward (P < 0.05). Western blotting analysis revealed that ligation of the femoral artery for 72 h increased the EP4 receptor protein in the L4 and L5 dorsal root ganglia over their freely perfused counterparts by 24% (P < 0.05). We conclude that EP4 receptors, but not EP3 receptors, play an important role in the exaggerated exercise pressor reflex found in rats with ligated femoral arteries. PMID:23568893

  6. Minimal basilar membrane motion in low-frequency hearing.

    PubMed

    Warren, Rebecca L; Ramamoorthy, Sripriya; Ciganović, Nikola; Zhang, Yuan; Wilson, Teresa M; Petrie, Tracy; Wang, Ruikang K; Jacques, Steven L; Reichenbach, Tobias; Nuttall, Alfred L; Fridberger, Anders

    2016-07-26

    Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the sound-evoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea. PMID:27407145

  7. Minimal basilar membrane motion in low-frequency hearing

    PubMed Central

    Warren, Rebecca L.; Ramamoorthy, Sripriya; Ciganović, Nikola; Zhang, Yuan; Wilson, Teresa M.; Petrie, Tracy; Wang, Ruikang K.; Jacques, Steven L.; Reichenbach, Tobias; Nuttall, Alfred L.; Fridberger, Anders

    2016-01-01

    Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the sound-evoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea. PMID:27407145

  8. Characterization of NPY receptors mediating contraction in rat intramyocardial coronary arteries.

    PubMed

    Prieto, D; García-Sacristán, A; Simonsen, U

    1998-09-25

    In vitro experiments in a microvascular myograph were designed in order to characterize the receptor subtypes and the mechanisms underlying the contractions induced by neuropeptide Y (NPY) in rat coronary small arteries. The rank order of potency for NPY-receptor agonist-induced increases in tension in endothelium-intact preparations was polypeptide Y (PYY)> NPY > or = [Leu31Pro34]NPY, while NPY(13-36) only induced small contractions at the highest concentration applied. The selective neuropeptide Y1 receptor antagonist, BIBP 3226, caused rightward shifts in the concentration-response curves for NPY and the slope of the Schild plot was not significantly different from unity. The pA2 value for BIBP 3226 against NPY was 7.88+/-0.15 (n = 6). We have earlier shown that endothelial cell removal does not change the contractile responses induced by NPY, but indomethacin (3 x 10(-6) M) significantly reduced the contractions induced by the peptide. In contrast, the thromboxane receptor antagonist, SQ29548, which abolished the contractions induced by the thromboxane analogue, U46619, did not change the concentration-response curves for NPY. In conclusion, the present study suggests that Y1 receptors mediate NPY-induced contractions in rat coronary resistance arteries, and that a non-thromboxane prostanoid is involved in the contractile mechanism.

  9. Effects of calcium and potassium supplements on arterial tone in vitro in spontaneously hypertensive rats

    PubMed Central

    Tolvanen, Jari-Petteri; Mäkynen, Heikki; Wu, Xiumin; Hutri-Kähönen, Nina; Rsukoaho, Heikki; Karjala, Kirsi; Pörsti, Ilkka

    1998-01-01

    Calcium and potassium intakes inversely correlate with blood pressure in experimental hypertension. Therefore, we examined the effects of calcium and potassium supplements alone and in combination on arterial tone in spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats served as normotensive controls. Calcium and potassium contents in the control diet were both 1%, while those in supplemented chows were 3% and 3.5%, respectively. The sodium content of all diets was moderately elevated to 1.1%.After 12 weeks of the study systolic blood pressures in SHR on high calcium and on high potassium diets were markedly lower (about 53 and 58 mmHg, respectively) than in hypertensive controls, while combined supplementation of these cations reduced blood pressure even further (about 69 mmHg).Responses of mesenteric arterial rings in vitro were examined at the end of the study. Both high calcium and high potassium diets improved the impaired relaxation to acetylcholine (ACh) in SHR, while the combination of these supplements completely normalized this response. Cyclo-oxygenase inhibition by diclofenac augmented the relaxation to ACh in hypertensive controls but not in the other groups. Nevertheless, enhanced endothelium-mediated dilatation was still observed in the presence of diclofenac and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in all supplemented groups. Interestingly, additional blockade of Ca2+-activated K+ channels by tetraethylammonium abolished the improved relaxation to ACh in SHR on high calcium and on high potassium, but distinct responses were still observed in WKY rats and SHR on the combined supplement.When hyperpolarization of smooth muscle was prevented by precontraction of the preparations with 50 mM KCl, only marginal differences were observed in the diclofenac and L-NAME-resistant relaxations to ACh between the study groups. Finally, endothelium-independent vasorelaxations of noradrenaline

  10. Microvascular anastomosis using fibrin glue and venous cuff in rat carotid artery.

    PubMed

    Sacak, Bulent; Tosun, Ugur; Egemen, Onur; Sakiz, Damlanur; Ugurlu, Kemal

    2015-04-01

    Conventional anastomosis with interrupted sutures can be time-consuming, can cause vessel narrowing, and can lead to thrombosis at the site of repair. The amount of suture material inside the lumen can impair the endothelium of the vessel, triggering thrombosis. In microsurgery, fibrin sealants have the potential beneficial effects of reducing anastomosis time and promoting accurate haemostasis at the anastomotic site. However, there has been a general reluctance to use fibrin glue for microvascular anastomoses because the fibrin polymer is highly thrombogenic and may not provide adequate strength. To overcome these problems, a novel technique was defined for microvascular anastomosis with fibrin glue and a venous cuff. Sixty-four rats in two groups are included in the study. In the experimental group (n = 32), end-to-end arterial anastomosis was performed with two stay sutures, fibrin glue, and a venous cuff. In the control group (n = 32), conventional end-to-end arterial anastomosis was performed. Fibrin glue assisted anastomosis with a venous cuff took less time, caused less bleeding at the anastomotic site, and achieved a patency rate comparable to that provided by the conventional technique. Fibrin sealant assisted microvascular anastomosis with venous cuff is a rapid, easy, and reliable technique compared to the end-to-end arterial anastomosis.

  11. Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats.

    PubMed

    Nevala, Riikka; Lassila, Markus; Finckenberg, Piet; Paukku, Kirsi; Korpela, Riitta; Vapaatalo, Heikki

    2002-09-27

    The aim of the present study was to evaluate the vascular effects of genistein in a short-term study. The ovariectomized spontaneously hypertensive rats (SHR) were divided into four groups (n = 8 in each), which received the following subcutaneous treatments either for 2 days or for 2 weeks: (1) solvent control (96% dimethylsulphoxide (DMSO) 1 ml/kg), (2) estradiol-17beta (25 microg/kg), (3) genistein (2.5 mg/kg; low-dose), and (4) genistein (25 mg/kg; high-dose). The renal arterial rings were studied using organ bath system. The renal artery contractions were attenuated by the 2-day low-dose genistein treatment as follows: angiotensin II (46%), noradrenaline (42%) KCl (36%), and endothelin-1 (34%). Only the angiotensin II-induced contractions were reduced by the 2-week treatment with estradiol-17beta (38%) and with the low-dose of genistein (31%). The 2-day genistein treatment reduced tyrosine phosphorylation, while the other treatments or treatment times had no effect. The 2-day low-dose genistein treatment had no estrogenic effect on the uterine morphology. The mechanism for attenuated contractility in the renal arteries after the 2-day low-dose genistein treatment is independent of the estrogenic effect of genistein, but is due to the tyrosine kinase inhibitory property of genistein.

  12. Effects of Venous Superdrainage and Arterial Supercharging on Dorsal Perforator Flap in a Rat Model

    PubMed Central

    Zheng, Jun; Xi, Shanshan; Ding, Maochao; Li, Hong; Xu, Wei; Tang, Maolin; Chen, Shixin

    2016-01-01

    Objective To comparatively assess the effects of venous superdrainage and arterial supercharging on dorsal perforator flap survival. Materials and Methods Sixty male Sprague-Dawley rats (450–550g) were randomly divided into three groups (n = 20), including control group (Control) and experimental groups A (venous superdrainage, Exp. A) and B (arterial supercharging, Exp. B). At postoperative day 7, survival areas of the flaps were evaluated and all animals underwent angiography. Laser Doppler was used to evaluate flap perfusion from 0h to 7days after surgery. Histology with hematoxylin and eosin staining was used to count microvessels. Tissue of “Choke vessels”was excised for quantification of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) by western blot assay at 6h and 7days after surgery. Results In the Exp. A group, almost all flaps survived (98.2±1.6%); in the Exp. B and control group, survival areas accounted for 78.8±8.5% and 60.3±7.8%, respectively (P <0.001). In addition, Exp. A animals showed improved anastomosis of choke vessels 2 compared with the Exp. B and Control groups. Furthermore, flap blood flow and partial pressure of oxygen in the Exp. A group were significantly higher compared with values obtained for the Exp. B and Control groups, from 6 hours to 7 days after surgery. More microvessels were found in the Exp. A group (11.65±1.33) than in Exp. B (9.25±0.34) and control (7.25±0.91) animals on POD 7. The relative expression level of HIF-1α and VEGF were significant at 6h and 7days after surgery. Conclusions Venous superdrainage in rat dorsal perforator flap is more effective than arterial supercharging in promoting flap survival, and could effectively alter hemodynamics in the microcirculation and stimulate blood vessel formation. PMID:27513520

  13. Automated detection of arterial input function in DSC perfusion MRI in a stroke rat model

    NASA Astrophysics Data System (ADS)

    Yeh, M.-Y.; Lee, T.-H.; Yang, S.-T.; Kuo, H.-H.; Chyi, T.-K.; Liu, H.-L.

    2009-05-01

    Quantitative cerebral blood flow (CBF) estimation requires deconvolution of the tissue concentration time curves with an arterial input function (AIF). However, image-based determination of AIF in rodent is challenged due to limited spatial resolution. We evaluated the feasibility of quantitative analysis using automated AIF detection and compared the results with commonly applied semi-quantitative analysis. Permanent occlusion of bilateral or unilateral common carotid artery was used to induce cerebral ischemia in rats. The image using dynamic susceptibility contrast method was performed on a 3-T magnetic resonance scanner with a spin-echo echo-planar-image sequence (TR/TE = 700/80 ms, FOV = 41 mm, matrix = 64, 3 slices, SW = 2 mm), starting from 7 s prior to contrast injection (1.2 ml/kg) at four different time points. For quantitative analysis, CBF was calculated by the AIF which was obtained from 10 voxels with greatest contrast enhancement after deconvolution. For semi-quantitative analysis, relative CBF was estimated by the integral divided by the first moment of the relaxivity time curves. We observed if the AIFs obtained in the three different ROIs (whole brain, hemisphere without lesion and hemisphere with lesion) were similar, the CBF ratios (lesion/normal) between quantitative and semi-quantitative analyses might have a similar trend at different operative time points. If the AIFs were different, the CBF ratios might be different. We concluded that using local maximum one can define proper AIF without knowing the anatomical location of arteries in a stroke rat model.

  14. Histological and Morphometric Analyses for Rat Carotid Artery Balloon Injury Studies

    PubMed Central

    Tulis, David Anthony

    2010-01-01

    i. Summary Experiments aimed at analyzing the response of blood vessels to mechanical injury and ensuing remodeling responses often employ the highly characterized carotid artery balloon injury model in laboratory rats. This approach utilizes luminal insertion of a balloon embolectomy catheter into the common carotid artery with inflation and withdrawal resulting in an injury characterized by vascular endothelial cell (EC) denudation and medial wall distension. The adaptive response to this injury is typified by robust vascular smooth muscle cell (SMC) replication and migration, SMC apoptosis and necrosis, enhanced synthesis and deposition of extracellular matrix (ECM) components, partial vascular EC regeneration from the border zones, luminal narrowing and establishment of a neointima in time-dependent fashion. Evaluation of these adaptive responses to blood vessel injury can include acute and longer-term qualitative and quantitative measures including expression analyses, activity assays, immunostaining for a plethora of factors and signals, and morphometry of neointima formation and gross mural remodeling. This chapter presents a logical continuation of Chapter    in this series that offers details for performing the rat carotid artery balloon injury model in a standard laboratory setting by providing commonly used protocols for performing histological and morphometric analyses in such studies. Moreover, procedures, caveats, and considerations included in this chapter are highly relevant for alternative animal vascular physiology/pathophysiology studies and in particular those related to mechanisms of vascular injury and repair. Included in this chapter are specifics for in situ perfusion-fixation, tissue harvesting and processing for both snap-frozen and paraffin-embedded protocols, specimen embedding and sectioning, slide preparation, several standard histological staining steps, and routine morphological assessment. Included in Notes are important caveats

  15. Impaired endothelial relaxations induced by agonists and flow in spontaneously hypertensive rat compared to Wistar-Kyoto rat perfused coronary arteries.

    PubMed

    Pourageaud, F; Freslon, J L

    1995-01-01

    The study was designed to compare the effects of agonists and flow on endothelial reactivity in perfused coronary arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. To this end, coronary arteries were cannulated at both ends using an arteriograph system. In the absence of flow and under an intraluminal pressure of 30 mm Hg, SHR arteries had larger internal diameters compared to those of WKY rats (275 +/- 10 vs. 239 +/- 7 microns, p < 0.01). In preparations preconstricted with serotonin HT, concentration-effect curves were constructed by adding acetylcholine or bradykinin in the bath. On the other hand, the effect of a stepwise increase in intraluminal flow (50-450 microliters/min) of physiological salt solution was observed. Agonist-induced dilations were significantly smaller in arteries of SHRs compared to those of WKY rats. Starting flow at the plateau of constriction led to dilations that were also weaker in SHR compared to WKY vessels: 27 +/- 6 vs. 61 +/- 3, p < 0.001, when expressed as percentage of maximal initial constrictions. The maximal dilation induced by flow in SHR arteries was obtained for a greater value of shear stress compared to that determined in WKY preparations: 81 +/- 6 vs. 60 +/- 4 dyn/cm2, p < 0.01. After endothelium destruction, flow-induced dilation was totally abolished in SHR arteries but only reduced in those of WKY rats. Subsequent additions of sodium nitroprusside induced complete dilations in vessels from both strains. The same protocol was performed in arteries submitted to a perfusion pressure of 90 mm Hg. In these conditions, impairments of agonist- and flow-induced dilations were also evidenced in SHR arteries. These results show that both the endothelium-dependent dilation induced by acetylcholine or bradykinin and the flow-induced dilation are impaired in coronary arteries of SHRs compared to WKY rats. These alterations appear to be due to a deterioration of endothelial cell function in the

  16. Material coefficients of the strain energy function of pulmonary arteries in normal and cigarette smoke-exposed rats.

    PubMed

    Liu, S Q; Fung, Y C

    1993-11-01

    The effect of cigarette smoke on the stress-strain relationship of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times daily with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The mechanical properties of the pulmonary arteries about 450 microns in external diameter (at zero pressure) were determined in vitro by inflation and deflation tests. The average stress and middle-wall strain of the selected pulmonary arteries were determined on the basis of experimental data including inflation and deflation pressures during loading and unloading processes, respectively, and vessel diameter and length at various pressure levels, and vessel circumferential and longitudinal lengths at zero-stress state. A constitutive equation for the pulmonary arteries was derived from an energy function depending on circumferential and longitudinal Green's strains. The coefficients of the strain energy function of the pulmonary arteries were determined in both the smoke-exposed and control rats by fitting the experimental stress-strain data with the constitutive equation. It was found that the wall stress of the pulmonary arteries at a given strain and most of the coefficients of the strain energy function were increased in both the 2- and 3-month smoke-exposed rats in comparison with those in the corresponding controls. These results indicated that cigarette smoke induced an increase in the wall stiffness of the pulmonary arteries in the rats. PMID:8262988

  17. Effect of engineered nanoparticles on vasomotor responses in rat intrapulmonary artery

    SciTech Connect

    Courtois, Arnaud; Andujar, Pascal; Ladeiro, Yannick; Ducret, Thomas; Rogerieux, Francoise; Lacroix, Ghislaine; Baudrimont, Isabelle; Guibert, Christelle; Roux, Etienne; Canal-Raffin, Mireille; Brochard, Patrick; Marano, Francelyne; Marthan, Roger; Muller, Bernard

    2010-06-01

    Pulmonary circulation could be one of the primary vascular targets of finest particles that can deeply penetrate into the lungs after inhalation. We investigated the effects of engineered nanoparticles on vasomotor responses of small intrapulmonary arteries using isometric tension measurements. Acute in vitro exposure to carbon nanoparticles (CNP) decreased, and in some case abolished, the vasomotor responses induced by several vasoactive agents, whereas acute exposure to titanium dioxide nanoparticles (TiO{sub 2}NP) did not. This could be attributed to a decrease in the activity of those vasoactive agents (including PGF{sub 2{alpha}}, serotonin, endothelin-1 and acetylcholine), as suggested when they were exposed to CNP before being applied to arteries. Also, CNP decreased the contraction induced by 30 mM KCl, without decreasing its activity. After endoplasmic reticulum calcium stores depletion (by caffeine and thapsigargin), CaCl{sub 2} addition induced a contraction, dependent on Store-Operated Calcium Channels that was not modified by acute CNP exposure. Further addition of 30 mM KCl elicited a contraction, originating from activation of Voltage-Operated Calcium Channels that was diminished by CNP. Contractile responses to PGF{sub 2{alpha}} or KCl, and relaxation to acetylcholine were modified neither in pulmonary arteries exposed in vitro for prolonged time to CNP or TiO{sub 2}NP, nor in those removed from rats intratracheally instilled with CNP or TiO{sub 2}NP. In conclusion, prolonged in vitro or in vivo exposure to CNP or TiO{sub 2}NP does not affect vasomotor responses of pulmonary arteries. However, acute exposure to CNP decreases contraction mediated by activation of Voltage-Operated, but not Store-Operated, Calcium Channels. Moreover, interaction of some vasoactive agents with CNP decreases their biological activity that might lead to misinterpretation of experimental data.

  18. Unique gene program of rat small resistance mesenteric arteries as revealed by deep RNA sequencing

    PubMed Central

    Reho, John J; Shetty, Amol; Dippold, Rachael P; Mahurkar, Anup; Fisher, Steven A

    2015-01-01

    Deep sequencing of RNA samples from rat small mesenteric arteries (MA) and aorta (AO) identified common and unique features of their gene programs. ∼5% of mRNAs were quantitatively differentially expressed in MA versus AO. Unique transcriptional control in MA smooth muscle is suggested by the selective or enriched expression of transcription factors Nkx2-3, HAND2, and Tcf21 (Capsulin). Enrichment in AO of PPAR transcription factors and their target genes of mitochondrial function, lipid metabolism, and oxidative phosphorylation is consistent with slow (oxidative) tonic smooth muscle. In contrast MA was enriched in contractile and calcium channel mRNAs suggestive of components of fast (glycolytic) phasic smooth muscle. Myosin phosphatase regulatory subunit paralogs Mypt1 and p85 were expressed at similar levels, while smooth muscle MLCK was the only such kinase expressed, suggesting functional redundancy of the former but not the latter in accordance with mouse knockout studies. With regard to vaso-regulatory signals, purinergic receptors P2rx1 and P2rx5 were reciprocally expressed in MA versus AO, while the olfactory receptor Olr59 was enriched in MA. Alox15, which generates the EDHF HPETE, was enriched in MA while eNOS was equally expressed, consistent with the greater role of EDHF in the smaller arteries. mRNAs that were not expressed at a level consistent with impugned function include skeletal myogenic factors, IKK2, nonmuscle myosin, and Gnb3. This screening analysis of gene expression in the small mesenteric resistance arteries suggests testable hypotheses regarding unique aspects of small artery function in the regional control of blood flow. PMID:26156969

  19. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

    PubMed

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.

  20. Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model

    PubMed Central

    Li, Xiaolong; Lu, Yan; Sun, Yi; Zhang, Qi

    2015-01-01

    Objective: Our objective is to explore the effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. Methods: 45 healthy male Wistar rats of clean grade were selected and divided into treatment group, model control group and blank control group. The rats in the treatment group and model control group received high-fat diet for 12 weeks and intraperitoneal injection of VD3 to establish rat coronary atherosclerosis heart disease model. After modeling, the rats in the treatment group received gavage of 100 mg/(kg·d) curcimin, and the rats in the model control group and blank control group received gavage of 5 ml/(kg·d) distilled water, the intervention time was 4 weeks. After intervention, the rats were killed, and the hearts were dissected to obtain the samples of coronary artery. After embedding and frozen section, immunofluorescence method was used to detect the change of endarterium permeability in 3 groups, Western blot was used to detect matrix metalloproteinase-9 (MMP-9) and CD40L in coronary artery tissue, and enzyme linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α) and C reaction protein (CRP). Results: After modeling, compared with the blank control group, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-c) in the treatment group and model control group were significantly higher (P<0.05), however, high density lipoprotein cholesterin (HDL-c) was significantly lower. The pathological sections showed that there was lipidosis in rat coronary artery in treatment group and model control group, indicating that the modeling was successful. Immunofluorescence showed that there was only a little fluorochrome permeability in artery in blank control group, there was some fluorochrome permeability in artery in the treatment group and there was a lot of fluorochrome permeability in artery in the model

  1. Quantitative electroencephalography spectral analysis and topographic mapping in a rat model of middle cerebral artery occlusion.

    PubMed

    Lu, X C; Williams, A J; Tortella, F C

    2001-12-01

    Electroencephalography (EEG) has a long history in clinical evaluations of cerebrovascular disease. Distinct EEG abnormalities, such as increased slow delta activity, voltage depression and epileptiform discharge, have been identified in stroke patients. However, preclinical use of EEG analysis of cerebral ischaemia is less documented. We report a new rat model of EEG topographic mapping during permanent and transient middle cerebral artery occlusion. Ten EEG electrodes were implanted on the rat skull, symmetrically covering the cortical regions of two hemispheres. Monopolar EEG recordings were acquired from each animal at multiple time points during the initial 24 h, and again once daily for 7 days. Traditional EEG examinations, quantitative EEG (qEEG) spectral analysis and topographic EEG mapping were employed for comprehensive data analyses. Several distinct spatiotemporal EEG abnormalities were identified in the ischaemic rat brain. In the ipsilateral hemisphere, pronounced increase in delta activity was observed in each recorded area within 24 h of injury. While sharp waves and spike complexes dominated the parietal region, a nearly isoelectric EEG state was seen in the temporal region. After 48 h, spontaneous, albeit incomplete, recovery of EEG activities developed in all rats. Reperfusion appeared to promote delta and alpha recovery more efficiently. The contralateral EEG changes were also recorded in two phases: an acute moderate increase in delta activities with intermittent rhythmic activities, followed by a delayed and significant increase in beta activities across the hemisphere. The similarities of rat qEEG profiles identified in this study to that of stroke patients and the application of topographic mapping broaden our research technology for preclinical experimental studies of brain injury.

  2. Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress.

    PubMed

    Liang, Ying; Wang, Jian; Gao, Haiqing; Wang, Quanzhen; Zhang, Jun; Qiu, Jie

    2016-10-01

    Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red‑victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin‑1 (ET‑1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension‑induced arterial remodeling, which was not associated with blood pressure control. ET‑1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension‑induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti‑arterial remodeling agent for patients with hypertensive vascular diseases. PMID:27601315

  3. Immunohistochemical localization of angiotensin II receptor types 1 and 2 in the mesenteric artery from spontaneously hypertensive rats.

    PubMed

    Diniz, Carmen; Leal, Sandra; Logan, Karen; Rocha-Pereira, Carolina; Soares, Ana Sofia; Rocha, Eduardo; Gonçalves, Jorge; Fresco, Paula

    2007-08-01

    Angiotensin II plays a crucial role in the control of blood pressure, acting at AT1 or AT2 receptors, and can act as a potent vasoconstrictor of the peripheral vasculature inducing hypertrophy, hyperplasia, or both, in resistance arteries. The aim of the present study was to investigate whether the pattern of distribution of angiotensin AT1 and AT2 receptors on mesenteric artery sections differs in spontaneously hypertensive rats (SHR) versus their respective controls (Wistar-Kyoto [WKY] rats). Immunohistochemistry using anti-AT1 or anti-AT2 antibodies was performed on perfused-fixed/paraffin-embedded mesenteric arteries from SHR and WKY rats. 3,3'-Diaminobenzidine tetrahydrochloride (DAB; activated by hydrogen peroxide) staining revealed distinct AT1 and AT2 labeling of all artery layers (adventitia, media and intima) from WKY rats, whereas in SHR an abundant AT1 labeling was found in both intima and adventitia and a sparser labeling in the media. There was a vast reduction of AT2 labeling throughout all layers. These results suggest a crucial role for AT2 receptors in the pathogenesis of hypertension.

  4. Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion.

    PubMed

    Zhang, Benping; Li, Feng; Zhao, Weijiang; Li, Jiebing; Li, Qingsong; Wang, Weizhi

    2015-09-01

    Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects.

  5. Histamine H(3) receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries.

    PubMed

    Sun, Pengyuan; Takatori, Shingo; Jin, Xin; Koyama, Toshihiro; Tangsucharit, Panot; Li, Simin; Zamami, Yoshito; Kitamura, Yoshihisa; Kawasaki, Hiromu

    2011-03-25

    The rat mesenteric artery has been shown to be innervated by adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. The present study was designed to investigate the involvement of histamine H(3) receptors in the neurotransmission of perivascular adrenergic and CGRPergic nerves. The mesenteric vascular beds without an endothelium isolated from male Wistar rats were perfused with Krebs solution and perfusion pressure was measured. In preparations with resting tension, the selective H(3) receptor agonist (R)-α-methylhistamine (α-methylhistamine; 10-100nM) significantly reduced periarterial nerve stimulation (2-8Hz)-induced vasoconstriction and noradrenaline release in the perfusate without an effect on the vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0nmol). In preparations with active tone produced by methoxamine (2μM) and in the presence of guanethidine (5μM), the periarterial nerve stimulation (1, 2Hz)-induced vasodilator response was inhibited by α-methylhistamine (0.1-1μM) perfusion without affecting vasodilation induced by exogenously injected CGRP (5pmol). Clobenpropit (histamine H(3) receptor antagonist, 1μM) canceled the α-methylhistamine-induced decrease in the periarterial nerve stimulation-induced vasoconstriction and noradrenaline release and periarterial nerve stimulation-induced vasodilation. These results suggest that the stimulation of H(3) receptors located in rat perivascular nerves inhibits presynaptically the neurotransmission of not only adrenergic nerves, but also CGRP nerves, by decreasing neurotransmitters.

  6. Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion.

    PubMed

    Zhang, Benping; Li, Feng; Zhao, Weijiang; Li, Jiebing; Li, Qingsong; Wang, Weizhi

    2015-09-01

    Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects. PMID:26045182

  7. Activation of Central Angiotensin Type 2 Receptors by Compound 21 Improves Arterial Baroreflex Sensitivity in Rats With Heart Failure

    PubMed Central

    Gao, Juan; Zucker, Irving H.

    2014-01-01

    BACKGROUND In a previous study we demonstrated that central administration of compound 21 (C21), a nonpeptide AT2R agonist, inhibited sympathetic tone in normal rats. In this study, we hypothesized that C21 exerts a similar effect in rats with coronary ligation–induced heart failure (HF). METHODS C21 was intracerebroventricularly infused for 7 days by osmotic mini pump. Blood pressure (BP) and heart rate (HR) were recorded by radiotelemetry in the conscious state to measure spontaneous arterial baroreflex sensitivity. Urine was collected for measurement of norepinephrine excretion. On the last day of C21 treatment, renal sympathetic nerve activity, BP, and HR were directly recorded under anesthesia, and the induced arterial baroreflex sensitivity was evaluated. Protein expressions of neuronal nitric oxide synthase (nNOS) and angiotensin II type 1 receptor (AT1R) in the subfornical organ, paraventricular nucleus, rostral ventrolateral medulla, and nucleus tractus solitarius were determined by Western blot analysis. RESULTS C21-treated HF rats displayed significantly less norepinephrine excretion (2,385.6±121.1 vs. 3,677.3±147.6ng/24 hours; P < 0.05) and lower renal sympathetic nerve activity (50.2±1.9% of max vs. 70.9±8.2% of max; P < 0.05) than vehicle-treated HF rats. C21-treated rats also exhibited improved spontaneous arterial baroreflex sensitivity and induced arterial baroreflex sensitivity. Bolus intracerebroventricular injection of angiotensin II–evoked pressor and sympatho-excitatory responses were attenuated in the C21-treated HF rats, which displayed upregulated nNOS and downregulated AT1R expression in the subfornical organ, paraventricular nucleus, and rostral ventrolateral medulla. CONCLUSIONS Activation of central angiotensin II type 2 receptor AT2R by C21 suppresses sympathetic outflow in rats with HF by improving baroreflex sensitivity and may provide important benefit in the HF syndrome. PMID:24687998

  8. Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability

    PubMed Central

    Roy, Lisa A.; Haenzi, Barbara; Tsai, Shi-Yen; Kartje, Gwendolyn; Beech, John S.; Cash, Diana; Moon, Lawrence

    2016-01-01

    Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, obesity and diabetes. Accordingly, when evaluating therapies for stroke in animals, it is important to select a model with excellent face validity. Ischemic stroke accounts for 80% of all strokes, and the majority of these occur in the territory of the middle cerebral artery (MCA), often inducing infarcts that affect the sensorimotor cortex, causing persistent plegia or paresis on the contralateral side of the body. We demonstrate in this video a method for producing ischemic stroke in elderly rats, which causes sustained sensorimotor disability and substantial cortical infarcts. Specifically, we induce permanent distal middle cerebral artery occlusion (MCAO) in elderly female rats by using diathermy forceps to occlude a short segment of this artery. The carotid artery on the ipsilateral side to the lesion was then permanently occluded and the contralateral carotid artery was transiently occluded for 60 min. We measure the infarct size using structural T2-weighted magnetic resonance imaging (MRI) at 24 hr and 8 weeks after stroke. In this study, the mean infarct volume was 4.5% ± 2.0% (standard deviation) of the ipsilateral hemisphere at 24 hr (corrected for brain swelling using Gerriet’s equation, n = 5). This model is feasible and clinically relevant as it permits the induction of sustained sensorimotor deficits, which is important for the elucidation of pathophysiological mechanisms and novel treatments. PMID:26967269

  9. Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability.

    PubMed

    Wayman, Christina; Duricki, Denise A; Roy, Lisa A; Haenzi, Barbara; Tsai, Shi-Yen; Kartje, Gwendolyn; Beech, John S; Cash, Diana; Moon, Lawrence

    2016-02-23

    Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, obesity and diabetes. Accordingly, when evaluating therapies for stroke in animals, it is important to select a model with excellent face validity. Ischemic stroke accounts for 80% of all strokes, and the majority of these occur in the territory of the middle cerebral artery (MCA), often inducing infarcts that affect the sensorimotor cortex, causing persistent plegia or paresis on the contralateral side of the body. We demonstrate in this video a method for producing ischemic stroke in elderly rats, which causes sustained sensorimotor disability and substantial cortical infarcts. Specifically, we induce permanent distal middle cerebral artery occlusion (MCAO) in elderly female rats by using diathermy forceps to occlude a short segment of this artery. The carotid artery on the ipsilateral side to the lesion was then permanently occluded and the contralateral carotid artery was transiently occluded for 60 min. We measure the infarct size using structural T2-weighted magnetic resonance imaging (MRI) at 24 hr and 8 weeks after stroke. In this study, the mean infarct volume was 4.5% ± 2.0% (standard deviation) of the ipsilateral hemisphere at 24 hr (corrected for brain swelling using Gerriet's equation, n = 5). This model is feasible and clinically relevant as it permits the induction of sustained sensorimotor deficits, which is important for the elucidation of pathophysiological mechanisms and novel treatments.

  10. Arterial blood gases, pulmonary function and pathology in rats exposed to 0. 75 or 1. 0 ppM ozone

    SciTech Connect

    Pepelko, W.E.; Mattox, J.K.; Yang, Y.Y.

    1980-06-01

    Arterial blood gases, residual lung volume (RV), deflation pressure volume (PV) curves, pulmonary pathology and body weight changes were studied in rats exposed up to 14 days to either 0.75 or 1.0 ppM ozone. Arterial PO2 and body weights decreased progressively with length of exposure while PaCO2 and RV increased. The slope of the PV curve decreased in all groups exposed to ozone. Pathological changes in the lung increased in severity with concentration and length of exposure. The present findings have shown that arterial blood gas measurements represent a sensitive index of altered lung function in rats, a species very sensitive to ozone exposure.

  11. Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries

    PubMed Central

    Caracuel, Laura; Jiménez-Altayó, Francesc; Romo, Mónica; Márquez-Martín, Ana; Dantas, Ana P.; Vila, Elisabet

    2012-01-01

    Mesenteric ischemia/reperfusion (I/R) is associated with high rates of morbidity and mortality. We studied the effect of mesenteric I/R on structural and mechanical properties of rat mesenteric resistance artery (MRA) that, once disrupted, might impact the outcome of this devastating clinical condition. Superior mesenteric artery from Wistar–Kyoto rats was occluded (90 min) and reperfused (24 h). The effect of tezosentan, a dual endothelin (ET)-receptor antagonist, was studied in ischemic (IO) and sham-operated (SO) animals. MRA structure and mechanics were assessed by pressure myography. Nuclei distribution, elastin content and organization, collagen I/III and ET-1 expression, ET-1 plasma levels, superoxide anion (O2⋅−) production, and mRNA levels of NAD(P)H-oxidase subunits were measured. To assess ET-1 effects on O2⋅− production, MRA from non-operated rats were incubated in culture medium with ET-1. Mesenteric I/R increased MRA wall thickness (P < 0.05) and cross-sectional area (P < 0.05) but decreased wall stiffness (P < 0.05). Arterial remodeling was paralleled by enhancement of: (i) collagen I/III expression (P < 0.01), ET-1 expression (P < 0.05), and O2⋅− formation (P < 0.01) in the vessel wall; (ii) number of internal elastic lamina (IEL) fenestrae (P < 0.05); and (iii) plasma levels of ET-1 (P < 0.05). Moreover, ET-1 increased O2⋅− (P < 0.05) production in cultured MRA. Tezosentan prevented hypertrophic remodeling and collagen I/III deposition, and enhanced O2⋅− production, but it did not affect the decreased wall stiffness after mesenteric I/R. These results indicate that 90 min occlusion/24 h reperfusion induces hypertrophic remodeling of MRA linked to ET-1-mediated increase of collagen and O2⋅−. Decreased stiffness may be associated with increased number of IEL fenestrae. The resulting MRA remodeling, initially adaptive, might become maladaptive contributing to the pathology and poor

  12. Vinpocetine Attenuates Neointimal Hyperplasia in Diabetic Rat Carotid Arteries after Balloon Injury

    PubMed Central

    Peng, Wenhui; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Liu, Baoxin; Li, Xiankai; Li, Weiming; Xu, Yawei

    2014-01-01

    Background Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Materials and Methods Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Results Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Conclusions Vinpocetine attenuated neointimal formation in diabetic

  13. Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2015-01-01

    Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs. PMID:26640533

  14. Interlobular arteries from two-kidney, one-clip Goldblatt hypertensive rats exhibit impaired vasodilator response to epoxyeicosatrienoic acids

    PubMed Central

    Sporková, Alexandra; Reddy, N. Rami; Falck, John R.; Imig, John D.; Kopkan, Libor; Sadowski, Janusz; Červenka, Luděk

    2016-01-01

    Background Small renal arteries have a significant role in regulation of renal hemodynamics and blood pressure (BP). To study potential changes in regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the two-kidney, one-clip (2K1C) Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) which are believed to be involved in regulation of renal vascular function and BP. Two newly synthesized EET analogs were also examined. Methods Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine (PE), pressurized, and the effects of a 14,15-EET analog, native 14,15-EET, and 11,12-ether-EET-8ZE, an analog of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results In the arteries from non-clipped kidneys isolated in the maintenance phase of Goldblatt hypertension the maximal vasodilatory response to 14,15-EET analog was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4± 6.4% versus 80.4±6%, and for native EETs they were 41.7 ± 6.6 % versus 62.8 ± 4.4 % (P ≤ 0.05 for each difference). Conclusions We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal ANG II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2K1C Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension. PMID:27140711

  15. Detailed behavioral analysis reveals both task strategies and spatial memory impairments in rats given bilateral middle cerebral artery stroke.

    PubMed

    Cain, Donald P; Boon, Francis

    2003-05-16

    Middle cerebral artery occlusion (MCAO) impairs performance in the water maze task by rats. The purpose was to evaluate the effect of bilateral MCAO in naive and strategies-pretrained rats using a detailed behavioral analysis to further develop a water maze model of stroke. Rats were trained in either a simple swim-to-visible platform task or in a conventional spatial version with a hidden platform in the pool. In the visible platform task naive stroked rats were impaired because of a marked tendency to swim thigmotaxically on most trials. For the spatial learning experiment, some rats received Morris' water maze strategies pretraining prior to MCAO and subsequent spatial training to familiarize them with the general behavioral strategies required in the task. In the spatial learning task naive stroked rats had both strategies and spatial learning impairments but pretrained stroked rats were indistinguishable from sham controls on all behavioral measures. All stroked rats had comparable bilateral brain damage measured using a computerized volumetric measuring technique. These results indicate that in naive rats bilateral MCAO causes behavioral strategies impairments in the visible and hidden platform versions of the water maze as well as specific spatial learning impairments in the hidden platform version. The results also indicate that behavioral strategies pretraining allows stroked rats to acquire and remember sufficient strategies skills and spatial information to perform as well as sham controls during subsequent spatial training. These techniques appear to be capable of quantifying the effects of potentially protective treatments for stroke.

  16. Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells From the Brain After Intra-arterial Infusion in Rats.

    PubMed

    Khabbal, Joonas; Kerkelä, Erja; Mitkari, Bhimashankar; Raki, Mari; Nystedt, Johanna; Mikkonen, Ville; Bergström, Kim; Laitinen, Saara; Korhonen, Matti; Jolkkonen, Jukka

    2015-01-01

    Intra-arterial (IA) delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) has shown potential as a minimally invasive therapeutic approach for stroke. The aim of the present study was to determine the whole-body biodistribution and clearance of technetium-99m ((99m)Tc)-labeled rat and human BM-MSCs after IA delivery in a rat model of transient middle cerebral artery occlusion (MCAO) using single-photon emission computed tomography (SPECT). Our hypothesis was that xenotransplantation has a major impact on the behavior of cells. Male RccHan:Wistar rats were subjected to sham operation or MCAO. Twenty-four hours after surgery, BM-MSCs (2 × 10(6) cells/animal) labeled with (99m)Tc were infused into the external carotid artery. Whole-body SPECT images were acquired 20 min, 3 h, and 6 h postinjection, after which rats were sacrificed, and organs were collected and weighed for measurement of radioactivity. The results showed that the majority of the cells were located in the brain and especially in the ipsilateral hemisphere immediately after cell infusion both in sham-operated and MCAO rats. This was followed by fast disappearance, particularly in the case of human cells. At the same time, the radioactivity signal increased in the spleen, kidney, and liver, the organs responsible for destroying cells. Further studies are needed to demonstrate whether differential cell behavior has any functional impact.

  17. Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension.

    PubMed

    Liu, S Q

    1996-11-01

    The effect of hypoxic hypertension on the remodeling process of the elastic laminae of the rat hilar pulmonary arteries (PAs) was studied by electron microscopy. Rats were exposed to hypoxia (10% O2) for periods of 0.5, 2,6,12,48,96,144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PA wall tensile stress. The PA blood pressure increased rapidly within the first several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due to elevated blood pressure and then decreased after 48 h due to vessel wall thickening and returned to the control level after 4 days. In association with these changes, the elastic laminae, which appeared homogeneous in normal control rats, changed into structures composed of randomly oriented filaments and edematous contents with an increase in the volume during the early period of hypoxia and regained their homogeneous appearance and normal volume after 4 days. The changes in the elastic laminae were correlated with changes in the tensile stress. These changes were associated with a transient decrease in the stiffness of the PAs. In hypoxic rats given nifedipine, no change was found in the blood pressure, the tensile stress, or the structure of the elastic laminae of the PAs despite continuous exposure to hypoxia. These results suggested that altered tensile stress in the PA wall played a critical role in the initiation and regulation of structural changes in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension. PMID:8941540

  18. Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats

    PubMed Central

    Veitenheimer, Britta J.; Engeland, William C.; Guzman, Pilar A.; Fink, Gregory D.

    2012-01-01

    Forty-eight hours of water deprivation (WD) in conscious rats results in a paradoxical increase in mean arterial pressure (MAP). Previous studies suggest this may be due to increased sympathetic nerve activity (SNA). However, this remains to be investigated in conscious, freely behaving animals. The purpose of this study was to determine, in conscious rats, the role of the sympathetic nervous system (SNS) in mediating WD-induced increases in MAP and to identify which vascular beds are targeted by increased SNA. Each rat was chronically instrumented with a radiotelemetry transmitter to measure MAP and heart rate (HR) and an indwelling venous catheter for plasma sampling and/or drug delivery. MAP and HR were continuously measured during a 2-day baseline period followed by 48 h of WD and then a recovery period. By the end of the WD period, MAP increased by ∼15 mmHg in control groups, whereas HR did not change significantly. Chronic blockade of α1/β1-adrenergic receptors significantly attenuated the WD-induced increase in MAP, suggesting a role for global activation of the SNS. However, the MAP response to WD was unaffected by selective denervations of the hindlimb, renal, or splanchnic vascular beds, or by adrenal demedullation. In contrast, complete adrenalectomy (with corticosterone and aldosterone replaced) significantly attenuated the MAP response to WD in the same time frame as α1/β1-adrenergic receptor blockade. These results suggest that, in conscious water-deprived rats, the SNS contributes to the MAP response and may be linked to release of adrenocortical hormones. Finally, this sympathetically mediated response is not dependent on increased SNA to one specific vascular bed. PMID:22904160

  19. Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.

    PubMed

    Warshaw, D M; Mulvany, M J; Halpern, W

    1979-08-01

    We studied alterations in structural and mechanical properties of mesenteric arterial resistance vessels from young (6-week) and old (50-week) spontaneously hypertensive (SHR)and matched normotensive Wistar-Kyoto (WKY) rats. Emphasis was placed upon relating the active tension capabilities of these vessels to their smooth muscle cell content. Cylindrical segments, 0.7 mm long with internal diameters of 150 micrometer, were mounted in a myograph capable of recording circumferential vessel wall tension and dimensions. Comparisons of vessel morphology and mechanics were performed at a normalized internal circumference, L1,where active tension (delta T1) is near maximum. Arterial wall and medial hypertrophy were observed in young and old SHR. Since the percent smooth muscle cells within the media for SHR was similar to that of WKY, both increased smooth muscle cell and connective tissue content account for the medial hypertrophy. These differences in SHR vessels were reflected directly in their passive and active mechanical properties. Fully relaxed vessels from SHR were less compliant, and upon activation at L1 (high potassium depolarization), delta T1 was not different for young SHR and WKY, but values for old SHR were 35% greater (P less than 0.05) than for WKY. When relating the active force generation of the vessel to the actual smooth muscle cell area, values for smooth muscle cell stress (force/area) were similar for SHR and WKY at both ages. In addition, similarities were observed for active dynamic mechanical measurements of Young's modulus and half response time. Genetic hypertension in rats therefore appears to be associated with the development of increased vessel contractility determined by a greater number of smooth muscle cells which possess contractile properties similar to those of normotensive vessels.

  20. Abnormal expression of vesicular transport proteins in pulmonary arterial hypertension in monocrotaline-treated rats.

    PubMed

    Zhang, Hongliang; Luo, Qin; Liu, Zhihong; Wang, Yong; Zhao, Zhihui

    2015-03-01

    Intracellular vesicular transport is shown to be dysfunctional in pulmonary arterial hypertension (PAH). However, the expression of intracellular vesicular transport proteins in PAH remains unclear. To elucidate the possible role of these proteins in the development of PAH, the changes in the expressions of N-ethyl-maleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP), synaptosome-associated membrane protein 23 (SNAP23), type 2 bone morphogenetic receptor (BMPR2), caveolin-1 (cav-1), and endothelial nitric oxide synthase (eNOS) were examined in lung tissues of monocrotaline (MCT)-treated rats by real-time polymerase chain reaction and western blot analysis. In addition, caspase-3, also examined by western blot analysis, was used as an indicator of apoptosis. Our data showed that during the development of PAH, the expressions of NSF, α-SNAP, and SNAP23 were significantly increased before pulmonary arterial pressure started to increase and then significantly decreased after PAH was established. The expressions of BMPR2 and eNOS were similar to those of NSF, α-SNAP, and SNAP23; however, the expression of cav-1 was down-regulated after MCT treatment. Caspase-3 expression was increased after exposure to MCT. In conclusion, the expressions of NSF, α-SNAP, and SNPA23 changed greatly during the onset of PAH, which was accompanied by abnormal expressions of BMPR2, cav-1, and eNOS, as well as an increase in apoptosis. Thus, changes in NSF, α-SNAP, and SNAP23 expressions appear to be mechanistically associated with the development of PAH in MCT-treated rats. PMID:25630652

  1. Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate.

    PubMed

    Al Rasheed, N M; Al Sayed, M I; Al Zuhair, H H; Al Obaid, A R; Fatani, A J

    2001-04-01

    Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P< 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential.

  2. Nitric oxide lowers the calcium sensitivity of tension in the rat tail artery

    PubMed Central

    Tran, Nguyen N P; Spitzbarth, Esther; Robert, Alain; Giummelly, Philippe; Atkinson, Jeffrey; Capdeville-Atkinson, Christine

    1998-01-01

    Controversy exists as to whether a fall in the intracellular Ca2+ concentration ([Ca2+]i) is a requisite element of the vasodilatory response to nitric oxide (NO). We studied the effect of NO on the coupling between [Ca2+]i and vasoconstriction in arterial segments loaded with the [Ca2+]i-sensitive, intracellular dye fura-2. As data interpretation is equivocal when fura-2 is loaded into both endothelial and smooth muscle cells, we compared results from in vitro experiments on segments of the rat tail artery in which fura-2 and noradrenaline were applied on the luminal or adventitial side, and endothelium was removed ‘physically’ (rubbing or air) or ‘functionally’ (Nω-nitro-l-arginine methyl ester). The use of air perfusion to remove endothelium is of considerable benefit since it allows paired observations in a single tissue. Fura-2 loaded into endothelial cells but endothelial ‘contamination’ of the smooth muscle cell [Ca2+]i signal was minimal. Endogenous NO decreased vasoconstrictor responses to noradrenaline but had no effect on [Ca2+]i. Nitroglycerine decreased vasoconstrictor responses in a concentration-dependent fashion but had no effect on [Ca2+]i. In conclusion, NO causes vasodilatation via a mechanism which is downstream of [Ca2+]i mobilization. PMID:9490833

  3. The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries.

    PubMed

    Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor; Kaufman, Marc P

    2016-05-01

    Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral arterial disease in which a femoral artery is chronically ligated than it is in rats with freely perfused femoral arteries. The role played by the mechanically sensitive component of the exaggerated exercise pressor reflex in ligated rats is unknown. We tested the hypothesis that the mechano-gated channel inhibitor GsMTx4, a relatively selective inhibitor of mechano-gated Piezo channels, reduces the exercise pressor reflex in decerebrate rats with ligated femoral arteries. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the pressor response to Achilles tendon stretch (a purely mechanical stimulus) but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid (purely metabolic stimuli). Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced both the integrated pressor area (control 535 ± 21, GsMTx4 218 ± 24 mmHg·s; P < 0.01), peak pressor (control 29 ± 2, GsMTx4 14 ± 3 mmHg; P < 0.01), and renal sympathetic nerve responses to electrically induced intermittent hindlimb muscle contraction (a mixed mechanical and metabolic stimulus). The reduction of the integrated pressor area during contraction caused by GsMTx4 was greater in rats with ligated femoral arteries than it was in rats with freely perfused femoral arteries. We conclude that the mechanically sensitive component of the reflex contributes to the exaggerated exercise pressor reflex during intermittent hindlimb muscle contractions in rats with ligated femoral arteries. PMID:26921442

  4. Potentiation of the hyporeactivity induced by in vivo endothelial injury in the rat carotid artery by chronic treatment with fish oil.

    PubMed Central

    Joly, G. A.; Schini, V. B.; Hughes, H.; Vanhoutte, P. M.

    1995-01-01

    1. The present study investigates whether or not chronic feeding of rats with a diet enriched in fish oil affects the reactivity of balloon-injured carotid arteries. The left carotid arteries were injured in vivo by the repeated passage of a balloon catheter. Both the right (control artery) and the left carotid arteries were excised 24 h after the injury, and suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. 2. Phenylephrine evoked similar concentration-contraction curves in the right (control) carotid arteries without endothelium from control and fish oil-fed rats. Balloon injury decreased the contractility of carotid arteries to phenylephrine in both types of rats and the pEC50 for phenylephrine was significantly decreased in balloon-injured arteries from control rats compared to those obtained in arteries from fish oil-fed rats (pEC50 7.59 +/- 0.1 and 7.28 +/- 0.06, respectively) while maximal contractions were similar (1.93 +/- 0.15 g and 1.79 +/- 0.12 g, respectively). 3. The treatment of control right carotid arteries without endothelium with either NG-nitro-L-arginine (an inhibitor of nitric oxide synthase) or superoxide dismutase (which protects nitric oxide from degradation) did not affect significantly the contractions to phenylephrine in either group. In these preparations, methylene blue (an inhibitor of soluble guanylate cyclase) decreased slightly but significantly maximal contractions to phenylephrine in both groups. The treatment of balloon-injured carotid arteries with NG-nitro-L-arginine or methylene blue partly restored contractions to phenylephrine in arteries from both types of rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7670727

  5. Composition of connective tissues and morphometry of vascular smooth muscle in arterial wall of DOCA-salt hypertensive rats - In relation with arterial remodeling.

    PubMed

    Hayashi, Kozaburo; Shimizu, Emiko

    2016-05-01

    Hypertension (HT) was induced in Wistar rats aged 16 and 48 weeks by a deoxycortico-sterone acetate (DOCA)-salt procedure. Common carotid arteries were resected 16 weeks after, and their histological specimens were selectively stained for observations of collagen, elastin, and vascular smooth muscle (VSM) cells. Then, the fractions of collagen and elastin and their radial distributions, and the size and number of VSM cells were determined with an image analyzer. These results were compared with the results from age-matched, non-treated, normotensive (NT) animals and also with those from our previous biomechanical studies. In both age groups, there were no significant differences in the fractions of collagen and elastin, and the ratio of collagen to elastin content between HT and NT arteries. These results correspond well with our previous biomechanical results, which showed no significant difference in wall elasticity between HT and NT vessels. Moreover, in the innermost layer out of 4 layers bordered with thick elastic lamellae, the fraction of collagen was significantly greater in HT arteries than in NT ones, which is attributable to HT-related stress concentration in the layer. VSM cells were significantly hypertrophied and their content was increased by HT, although their total number in the media remained unchanged. The increased size and content of cells correspond to the enhancement of vascular tone and contractility in HT arteries. PMID:26987272

  6. Composition of connective tissues and morphometry of vascular smooth muscle in arterial wall of DOCA-salt hypertensive rats - In relation with arterial remodeling.

    PubMed

    Hayashi, Kozaburo; Shimizu, Emiko

    2016-05-01

    Hypertension (HT) was induced in Wistar rats aged 16 and 48 weeks by a deoxycortico-sterone acetate (DOCA)-salt procedure. Common carotid arteries were resected 16 weeks after, and their histological specimens were selectively stained for observations of collagen, elastin, and vascular smooth muscle (VSM) cells. Then, the fractions of collagen and elastin and their radial distributions, and the size and number of VSM cells were determined with an image analyzer. These results were compared with the results from age-matched, non-treated, normotensive (NT) animals and also with those from our previous biomechanical studies. In both age groups, there were no significant differences in the fractions of collagen and elastin, and the ratio of collagen to elastin content between HT and NT arteries. These results correspond well with our previous biomechanical results, which showed no significant difference in wall elasticity between HT and NT vessels. Moreover, in the innermost layer out of 4 layers bordered with thick elastic lamellae, the fraction of collagen was significantly greater in HT arteries than in NT ones, which is attributable to HT-related stress concentration in the layer. VSM cells were significantly hypertrophied and their content was increased by HT, although their total number in the media remained unchanged. The increased size and content of cells correspond to the enhancement of vascular tone and contractility in HT arteries.

  7. Effect of endogenous and exogenous nitric oxide on calcium sparks as targets for vasodilation in rat cerebral artery.

    PubMed

    Mandalà, Maurizio; Heppner, Thomas J; Bonev, Adrian D; Nelson, Mark T

    2007-02-01

    The potent vasodilator nitric oxide (NO), produced mainly by the endothelium, acts through a BK(Ca)-dependent mechanism to increase the frequency of calcium sparks (Ca(2+) sparks) in myocyte isolated from rat cerebral arteries. Our present aim has been to assess the role of endogenous and exogenous NO on the Ca(2+) sparks through ryanodine-sensitive channels in the sarcoplasmic reticulum of an intact artery. Calcium sparks, detected with fluo-4 and laser scanning confocal microscopy, were examined in isolated pressurized rat posterior cerebral arteries with (intact) and without endothelium (denuded). Addition of the NO donor, DEA-NONOate (N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine), did not change the amplitude and frequency of Ca(2+) sparks in the intact artery. However, inhibition of nitric oxide synthase with N-omega-nitro-L-arginine or removal of endothelium reduced Ca(2+) sparks frequency by about 50%. Under these conditions (i.e., absence of endogenous NO production), DEA-NONOate, increased Ca(2+) spark frequency 3- to 4-fold. These results suggest that endothelial NO modulates local Ca(2+) release events in the arterial smooth muscle and that this mechanism may contribute to the actions of nitrovasodilators.

  8. C60 Exposure Augments Cardiac Ischemia/Reperfusion Injury and Coronary Artery Contraction in Sprague Dawley Rats

    PubMed Central

    Holland, Nathan A.; Vidanapathirana, Achini K.; Pitzer, Joshua E.; Han, Li; Sumner, Susan J.; Lewin, Anita H.; Fennell, Timothy R.; Lust, Robert M.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    The potential uses of engineered C60 fullerene (C60) have expanded in recent decades to include industrial and biomedical applications. Based on clinical findings associated with particulate matter exposure and our data with multi-walled carbon nanotubes, we hypothesized that ischemia/reperfusion (I/R) injury and pharmacological responses in isolated coronary arteries would depend upon the route of exposure and gender in rats instilled with C60. Male and female Sprague Dawley rats were used to test this hypothesis by surgical induction of cardiac I/R injury in situ 24 h after intratracheal (IT) or intravenous (IV) instillation of 28 μg of C60 formulated in polyvinylpyrrolidone (PVP) or PVP vehicle. Serum was collected for quantification of various cytokines. Coronary artery segments were isolated for assessment of vasoactive pharmacology via wire myography. Both IV and IT exposure to C60 resulted in expansion of myocardial infarction in male and female rats following I/R injury. Serum-collected post-I/R showed elevated concentrations of interleukin-6 and monocyte chemotactic protein-1 in male rats exposed to IV C60. Coronary arteries isolated from male rats exposed to IT C60 demonstrated augmented vasocontraction in response to endothelin-1 that was attenuated with Indomethacin. IV C60 exposure resulted in impaired acetylcholine relaxation in male rats and IT C60 exposure resulted in depressed vasorelaxation in response to sodium nitroprusside in female rats. Based on these data, we conclude that IT and IV exposure to C60 results in unique cardiovascular consequences that may favor heightened coronary resistance and myocardial susceptibility to I/R injury. PMID:24431213

  9. The new NO donor Terpy induces similar relaxation in mesenteric resistance arteries of renal hypertensive and normotensive rats.

    PubMed

    Araújo, Alice V; Pereira, Amanda C; Grando, Marcella D; da Silva, Roberto S; Bendhack, Lusiane M

    2013-11-30

    The present work aimed to investigate the cellular mechanisms involved on the vasorelaxation induced by the new nitric oxide donor [Ru(terpy)(bdq)NO](3+) (Terpy) in isolated mesenteric resistance artery and to compare the vascular responses in isolated vessels from 2K and 2K-1C hypertensive rats. We have used this artery because it is important to the control of vascular resistance and consequently to the blood pressure control. The NO donor Terpy induced relaxation in a concentration-dependent way in mesenteric resistance arteries. There were no differences between renal hypertensive (2K-1C) and normotensive (2K) in Terpy-induced relaxation neither in NO released. The relaxation induced by Terpy was inhibited by the soluble guanylyl-cyclase (sGC) inhibitor ODQ both in 2K and in 2K-1C with similar amplitude. In agreement with these data, the protein expression of the subunits α1 and β1 of the enzyme sGC was not different between 2K-1C and 2K mesenteric bed. The relaxation induced by Terpy was inhibited by the cGMP-dependent protein kinase (G kinase) inhibitor or by the non-selective K(+) channel blocker tetraethylamonium (TEA), but with no difference between 2K-1C and 2K arteries. The relaxation induced by Terpy was also inhibited by the SERCA inhibitor thapsigargin in both groups. Taken together, these results show that the vascular relaxation induced by the NO donor [Ru(terpy)(bdq)NO](3+) involves the activation of NO/sGC/cGMP/GK pathway, activation of K(+) channels sensitive to TEA and SERCA in normotensive and renal hypertensive rat mesenteric resistance arteries. Surprisingly, Terpy-induced vasorelaxation is similar in mesenteric resistance arteries of renal hypertensive and normotensive rats.

  10. Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

    2010-03-01

    Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

  11. Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis

    PubMed Central

    Chang, Kuo-Chu; Su, Ming-Jai; Peng, Ying-I; Shao, Ching-Chih; Wu, Yang-Chang; Tseng, Yung-Zu

    2001-01-01

    In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10−7 g kg−1. The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10−7 g kg−1 had effects on the left ventricular (LV)-arterial coupling in Wistar rats. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (Ees) and effective arterial volume elastance (Ea), respectively. The optimal afterload (Qload) determined by the ratio of Ea to Ees was used to measure the optimality of energy transmission from the left ventricle to the arterial system. Liriodenine at the dose of 10−7 g kg−1 showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (Pes), Ea, Ees, and Qload. By contrast, liriodenine at the dose of 10−6 g kg−1 produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in Pes. Moreover, liriodenine administration of 10−6 g kg−1 to rats significantly decreased Ees by 8.5% and Ea by 10.6%, but did not change Qload. We conclude that liriodenine at the dose of 10−7 g kg−1 has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system. PMID:11325791

  12. L-Carnitine supplementation impairs endothelium-dependent relaxation in mesenteric arteries from rats.

    PubMed

    Valgas da Silva, Carmem P; Rojas-Moscoso, Julio A; Antunes, Edson; Zanesco, Angelina; Priviero, Fernanda B M

    2014-07-01

    L-Carnitine (L-Car) is taken as fat burner. The risks of L-Car supplementation for the cardiovascular system are unclear. We evaluated the relaxing responses of the mesenteric and aorta rings from rats after four weeks of L-Car supplementation and/or physical training. Concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as cyclic GMP levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) were evaluated. Physical training decreased body weight gain that was potentiated by L-Car. In mesenteric rings, L-Car impaired endothelium-dependent relaxation whereas endothelium independent relaxation was increased. In aorta, exercise improved endothelium-dependent relaxation; however, it was partially inhibited by L-Car. SNP-induced relaxation was similar in aorta of all groups. Basal cGMP were increased in aorta of exercised rats. SOD activity and MDA levels were unaltered. In conclusion, L-Car and physical exercise promotes body weight loss; however, it impairs endothelium-dependent vaso-relaxation possibly involving alterations in muscarinic receptors/eNOS/NO signalling pathway in mesenteric artery.

  13. Combination of Cilostazol and L-Carnitine Improves Walking Performance in Peripheral Arterial Disease Model Rats.

    PubMed

    Shiga, Toshinori; Sahara, Hiroeki; Orito, Kensuke

    2015-01-01

    Cilostazol and L-carnitine have been used as a first-line drug and supplement, respectively, in patients with peripheral arterial disease with intermittent claudication. In this study, the effect of the combination of cilostazol and L-carnitine has been investigated in rats with unilateral hindlimb ischemia. For 28 days, cilostazol and L-carnitine were administrated separately or as a combination. The distance walked before gait disturbance developed was measured using a treadmill for 5 days a week. The capillary density of the ischemic hindlimb was evaluated by immunohistochemical staining at days 7, 14, 21, and 28. Angiogenic gene expression was measured by real-time RT-PCR at days 7 and 28. The greatest increase in the distance was observed in the combination therapy group when compared to the other groups. The capillary density in the adductor muscles of rats treated with cilostazol alone and combination therapy increased at day 28. Angiopoietin-2/Angiopoietin-1 expression ratios were higher, suggesting the promotion of angiogenesis, with cilostazol alone and combination therapy at day 7. This is the first study to show functional improvement of the hind limb following combination therapy with cilostazol and L-carnitine in experimental animals. This study also revealed that cilostazol promotes angiogenesis, and L-carnitine additively contributes to functional improvement via a non-angiogenic mechanism.

  14. Age Impaired endothelium-dependent vasodilation is improved by resveratrol in rat mesenteric arteries

    PubMed Central

    Gocmez, Semil S; Scarpace, Philip J; Whidden, Melissa A; Erdos, Benedek; Kirichenko, Nataliya; Sakarya, Yasemin; Utkan, Tijen; Tumer, Nihal

    2016-01-01

    [Purpose] To determine whether resveratrol improves the adverse effects age on vascular function in mesenteric arteries (MAs), and diminishes the hyperactivity in adrenal gland with age. [Methods] Male F344 x Brown Norway rats were assigned to 6-month control (YC), 6-month resveratrol (YR), 24-month control (OC) and 24-month resveratrol (OR). Resveratrol (15 mg/kg) was provided to resveratrol groups in drinking water for 14 days. [Results] Concentration response curves to phenylephrine (PE, 10-9-10-5M), acetylcholine (Ach, 10-9-10-5M) and resveratrol (10-8-10-4M) were evaluated in pressurized isolated MAs. The Ach concentration-response curve was right shifted with maximal response diminished in OC compared with YC rats. These effects were reversed by resveratrol treatment. The resveratrol-mediated relaxant responses were unchanged with age or resveratrol suggesting an endothelium-independent mechanism. Resveratrol tended to increase endothelial nitric oxide synthase; caused no effect on copper-zinc superoxide dismutase; and normalized the age-related elevatation in DβH and NPY levels in adrenal medulla, two indicators of sympathetic activity [Conclusion] These data indicate that resveratrol reverses age-related dysfunction in endothelium-dependent vasodilation in MAs and partially reverses hyperactivity of adrenomedullary function with age. This treatment may have a therapeuticpotential in the treatment of cardiovascular diseases or hypertension in the elderly. PMID:27298812

  15. Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats.

    PubMed

    Li, Zhenlan; Hua, Cong; Pan, Xiaoqiang; Fu, Xijia; Wu, Wei

    2016-08-01

    Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury. PMID:27324156

  16. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

    PubMed

    Pinkham, Maximilian I; Whalley, Gillian A; Guild, Sarah-Jane; Malpas, Simon C; Barrett, Carolyn J

    2015-07-15

    There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI. PMID:25994953

  17. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

    PubMed

    Pinkham, Maximilian I; Whalley, Gillian A; Guild, Sarah-Jane; Malpas, Simon C; Barrett, Carolyn J

    2015-07-15

    There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.

  18. Acute and long-term effects of tissue culture on contractile reactivity in renal arteries of the rat.

    PubMed

    De Mey, J G; Uitendaal, M P; Boonen, H C; Vrijdag, M J; Daemen, M J; Struyker-Boudier, H A

    1989-10-01

    To evaluate long-term effects of contractile and mitogenic stimuli on the contractile reactivity of arterial smooth muscle, we measured the incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) and mechanical responses in arterial segments that had been maintained in tissue culture. The experiments were performed on renal arteries that had been isolated from adult rats, chemically sympathectomized, mechanically denuded from endothelium and mounted under distension. Exposure of arterial segments for up to 3 weeks to culture medium supplemented with fetal calf serum resulted in the following consecutive changes: a strong acute contraction, selective pharmacological changes that included decreased contractile responses to phenylephrine and vasopressin and increased relaxing responses to isoproterenol, increased incorporation of BrdUrd, a progressive fall in contractile responses to all vasoconstrictor stimuli, and an increase in excitability. Serum-free medium resulted in a much smaller acute arterial contraction, induced less incorporation of BrdUrd, accelerated the occurrence of hyperexcitability, but did not affect early pharmacological changes or the subsequent fall in overall arterial contractility with tissue culture. Dialysis of the serum or addition of ketanserin abolished the contractile effect of serum but did not affect the incorporation of BrdUrd or the loss of contractility with tissue culture. Addition of serotonin to serum-free culture medium mimicked the contractile response to serum but not the stimulation of BrdUrd incorporation. These data indicate that tissue culture alters the properties of the arterial wall, that contraction does not underlie the proliferative response of arterial smooth muscle to serum-derived mitogens in vitro, and that stimulation of DNA synthesis does in itself not lead to selective changes in arterial contractility.

  19. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  20. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  1. Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

    PubMed Central

    de Queiroz, D B; Sastre, E; Caracuel, L; Callejo, M; Xavier, F E; Blanco-Rivero, J; Balfagón, G

    2015-01-01

    Background and Purpose We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. Experimental Approach Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. Key Results Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. Conclusions and Implications The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats. PMID:26177571

  2. Tranilast Increases Vasodilator Response to Acetylcholine in Rat Mesenteric Resistance Arteries through Increased EDHF Participation

    PubMed Central

    Sastre, Esther; Caracuel, Laura; Callejo, María; Balfagón, Gloria

    2014-01-01

    Background and Purpose Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA). Experimental Approach Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholine-induced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K+ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619. Key Results Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K+ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilast-incubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast. Conclusions and Implications Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channels. PMID:24992476

  3. [Giant vertebro-basilar aneurysm. Frontal syndrome].

    PubMed

    Rosa, A; Mizon, J P; Sevestre, H

    1991-01-01

    A 72-year-old man presented with an apparent frontal syndrome. He also had bilateral trigeminal neuralgia, a pyramidal syndrome of all 4 limbs, balance disturbances, a horizontal nystagmus when looking to the left and a right velopalatine paralysis. CT scan with contrast showed a hyperdense rounded lesion in the left cerebello-pontine angle. Cerebral angiography showed this to be a large aneurysm of the end of the vertebral arteries. The patient died suddenly. Autopsy confirmed the site and presence of the aneurysm. Balance disturbances, the pyramidal syndrome and velopalatine paralysis could all be explained by brain stem compression and the bilateral nature of the trigeminal neuralgia by compression of the trigemino-thalamic tract. The apparent frontal syndrome, the authors suggest could have resulted from subacute raised intracranial pressure.

  4. Impaired endothelium-dependent relaxation in isolated resistance arteries of spontaneously diabetic rats.

    PubMed Central

    Heygate, K. M.; Lawrence, I. G.; Bennett, M. A.; Thurston, H.

    1995-01-01

    1. Previous studies have shown that endothelium-dependent relaxation in the aorta of spontaneously diabetic bio bred rats (BB) is impaired. 2. We have investigated noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) and bradykinin (BK) relaxation, and endothelium-independent sodium nitroprusside (SNP) relaxation in mesenteric resistance arteries of recent onset BB rats and established insulin treated BB rats, compared to their age-matched non diabetic controls. 3. There was no significant difference in the maximum contractile response or sensitivity to noradrenaline in either of the diabetic groups compared to their age-matched controls. 4. Incubation with the nitric oxide synthetase inhibitor NG-nitro-L-arginine (L-NOARG) resulted in a significant increase in maximum contractile response to noradrenaline in the recent onset age-matched control group (P < 0.05). Analysis of the whole dose-response curve (using ANOVA for repeated measures with paired t test) showed a significant left-ward shift following the addition of L-NOARG (P < 0.001). A similar but less marked shift (P < 0.01) was evident in vessels from recent onset diabetics. An overall shift in both sensitivity and maximum response was also evident in the age-matched non diabetic controls of the insulin-treated group (P < 0.05). However, by contrast, there was no significant change in sensitivity in the insulin-treated diabetic rats. 5. ACh-induced endothelium-dependent relaxation was significantly impaired in the recent onset diabetic rats compared to their age-matched controls (47 +/- 11% versus 92 +/- 2%, P < 0.05, n = 6), and in the insulin treated diabetic rats (34 +/- 5% versus 75 +/- 6%, P < 0.05, n = 6). The relaxation responses to BK also were significantly impaired in the diabetic rats compared to their age-matched controls (recent onset: 20 +/- 3% versus 72 +/- 7%, P < 0.05, n = 6; insulin treated: 12 +/- 9% versus 68 +/- 7%, P < 0.05, n = 7). 6. Incubation with either the

  5. Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y1-receptor in rat mesenteric small arteries

    PubMed Central

    Prieto, Dolores; Buus, Carsten L; Mulvany, Michael J; Nilsson, Holger

    2000-01-01

    Simultaneous measurements of intracellular calcium concentration ([Ca2+]i) and tension were performed to clarify whether the mechanisms which cause the neuropeptide Y (NPY)-elicited contraction and potentiation of noradrenaline contractions, and the NPY inhibition of forskolin responses are linked to a single or different NPY receptor(s) in rat mesenteric small arteries.In resting arteries, NPY moderately elevated [Ca2+]i and tension. These effects were antagonized by the selective Y1 receptor antagonist, (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginineamide (BIBP 3226) (apparent pKB values of 8.54±0.25 and 8.27±0.17, respectively).NPY (0.1 μM) caused a near 3 fold increase in sensitivity to noradrenaline but did not significantly modify the tension-[Ca2+]i relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA2 7.87±0.20).In arteries activated by vasopressin, the adenylyl cyclase activator forskolin (3 μM) induced a maximum relaxation and a return of [Ca2+]i to resting levels. NPY completely inhibited these effects. The contractile responses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forskolin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA2 of 7.92±0.29.Electrical field stimulation (EFS) at 8–32 Hz caused large contractions in arteries relaxed with either forskolin or noradrenaline in the presence of phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response.The present results suggest that different intracellular pathways are linked to a single NPY Y1 receptor in intact rat mesenteric small arteries, and provide

  6. Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y(1)-receptor in rat mesenteric small arteries.

    PubMed

    Prieto, D; Buus, C L; Mulvany, M J; Nilsson, H

    2000-04-01

    Simultaneous measurements of intracellular calcium concentration ([Ca(2+)](i)) and tension were performed to clarify whether the mechanisms which cause the neuropeptide Y (NPY)-elicited contraction and potentiation of noradrenaline contractions, and the NPY inhibition of forskolin responses are linked to a single or different NPY receptor(s) in rat mesenteric small arteries. In resting arteries, NPY moderately elevated [Ca(2+)](i) and tension. These effects were antagonized by the selective Y(1) receptor antagonist, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininea mide (BIBP 3226) (apparent pK(B) values of 8.54+/-0.25 and 8.27+/-0.17, respectively). NPY (0.1 microM) caused a near 3 fold increase in sensitivity to noradrenaline but did not significantly modify the tension-[Ca(2+)](i) relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA(2) 7.87+/-0.20). In arteries activated by vasopressin, the adenylyl cyclase activator forskolin (3 microM) induced a maximum relaxation and a return of [Ca(2+)](i) to resting levels. NPY completely inhibited these effects. The contractile responses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forskolin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA(2) of 7.92+/-0.29. Electrical field stimulation (EFS) at 8-32 Hz caused large contractions in arteries relaxed with either forskolin or noradrenaline in the presence of phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response. The present results suggest that different intracellular pathways are linked to a single NPY Y(1) receptor in intact rat

  7. Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats

    PubMed Central

    Fukao, Mitsuhiro; Hattori, Yuichi; Kanno, Morio; Sakuma, Ichiro; Kitabatake, Akira

    1997-01-01

    The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diabetes mellitus. Membrane potentials were recorded in mesenteric arteries from rats with streptozotocin-induced diabetes and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic mesenteric arteries (−55.3±0.5 vs −55.6±0.4 mV). However, endothelium-dependent hyperpolarization produced by acetylcholine (ACh; 10−8–10−5 M) was significantly diminished in amplitude in diabetic arteries compared with that in controls (maximum −10.4±1.1 vs −17.2±0.8 mV). Furthermore, the hyperpolarizing responses of diabetic arteries were more transient. ACh-induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3×10−4 M NG-nitro-L-arginine (L-NOARG), 10−5 M indomethacin or 60 u ml−1 superoxide dismutase. Endothelium-dependent hyperpolarization with 10−6 M A23187, a calcium ionophore, was also decreased in diabetic arteries compared to controls (−8.3±1.4 vs −18.0±1.9 mV). However, endothelium-independent hyperpolarizing responses to 10−6 M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (−20.0±1.4 vs −19.2±1.1 mV). The altered endothelium-dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium-dependent relaxations by ACh in the presence of 10−4 M L-NOARG and 10−5 M indomethacin in diabetic arteries were also reduced and more transient compared to controls. These data indicate that endothelium-dependent hyperpolarization is reduced by diabetes, and this would, in part, account for the impaired endothelium-dependent relaxations in mesenteric arteries from diabetic rats. PMID:9257918

  8. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Wietholt, Christian; Haworth, Steven T.; Dawson, Christopher A.

    2002-04-01

    In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model.

  9. Influence of hypertension on nitric oxide synthase expression and vascular effects of lipopolysaccharide in rat mesenteric arteries

    PubMed Central

    Briones, Ana M; Alonso, María J; Marín, Jesús; Balfagón, Gloria; Salaices, Mercedes

    2000-01-01

    Experiments were designed to investigate the effects of the inducible nitric oxide synthase (iNOS) stimulator, lipopolysaccharide (LPS), on noradrenaline (NA) responses and on NOS activity and its expression in intact mesenteric resistance arteries (MRAs) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In MRAs from WKY, LPS (10 μg ml−1; 1–5 h) reduced the vasoconstrictor responses to NA (0.1–30 μM) in the presence, but not in the absence of L-arginine (L-Arg, 10 μM). However, in SHR arteries, LPS induced an incubation-time dependent reduction of NA responses in the absence, as well as the presence, of L-Arg. The LPS inhibitory effect was reduced by the non-specific NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 μM) and the selective iNOS inhibitor, aminoguanidine (100 μM). L-NAME alone similarly shifted the concentration-response curve to NA leftward in arteries from both strains, while aminoguanidine had no effect. L-Arg shifted the curve to NA rightward only in SHR MRAs. Basal activity of both iNOS and constitutive NOS (conversion of [3H]-L-Arg to [3H]-L-citrulline) was similar in arteries from both strains. After 5 h incubation with LPS, only iNOS activity in arteries from SHR was increased. Basal iNOS protein expression was undetectable; basal endothelial (eNOS) protein expression was similar in arteries from both strains, while neuronal (nNOS) was greater in arteries from SHR. LPS induced iNOS protein expression, that was higher in arteries from SHR than in those from WKY. These results indicate that NO production, via iNOS induction, is greater than in those from MRAs from SHR to WKY. PMID:10991910

  10. Protective effect of melatonin on cigarette smoke-induced restenosis in rat carotid arteries after balloon injury.

    PubMed

    Yang, Gen-Huan; Li, Yan-Chuan; Wang, Zhan-Qi; Liu, Bao; Ye, Wei; Ni, Leng; Zeng, Rong; Miao, Shi-Ying; Wang, Lin-Fang; Liu, Chang-Wei

    2014-11-01

    Vascular restenosis after the interventional angioplasty remains the main obstacle to a favorable long-term patency. Many researches suggest cigarette smoking is one of the most important causes of restenosis. This study was designed to investigate whether melatonin could protect against the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury. Three groups of male rats (normal condition, cigarette smoke exposed, cigarette smoke exposed, and melatonin injected) were used in this study. An established balloon-induced carotid artery injury was performed, and the carotid arteries were harvested from these three groups 14 days later. The ratio of intima to media, the infiltration of inflammatory cells, the expression of inflammatory cytokines (NF-κB, IL-1β, IL-6, TNF-α, MCP-1), adhesion molecules (ICAM-1, VCAM-1), and eNOS were measured. The results showed that cigarette smoke exposure aggravated the stenosis of the lumen, promoted the infiltration of inflammatory cells and induced the expression of the inflammatory cytokines and adhesion molecules after the balloon-induced carotid artery injury. Moreover, cigarette smoke exposure can inhibit the expression of eNOS. Particularly, we surprised that melatonin could minimize this effect caused by cigarette smoke. These results suggested that melatonin could prevent the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury and the mechanism of its protective effect may be the inhibition of the inflammatory reaction. This also implies melatonin has the potential therapeutic applicability in prevention of restenosis after the vascular angioplasty in smokers.

  11. COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

    PubMed

    Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

    2015-07-01

    Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS.

  12. Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed a high-fat, high-sucrose, Western pattern diet.

    PubMed

    La Favor, Justin D; Anderson, Ethan J; Hickner, Robert C; Wingard, Christopher J

    2013-03-01

    Introduction.  It is suggested that erectile dysfunction (ED) may be an early risk factor for cardiovascular disease. Aim.  The goal of this study was to determine whether development of ED precedes the onset of coronary artery endothelial dysfunction in response to a Western diet (WD), thereby establishing whether the WD differentially impacts the endothelium in a time-dependent manner. Additionally, a goal was to determine if diet-induced ED is reversible with intracavernosal sepiapterin treatment. Methods.  Male Sprague-Dawley rats were fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to electrical field stimulation of the cavernosal nerve near the major pelvic ganglion, in the absence and presence of sepiapterin. Coronary artery endothelial function was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to segments of the left anterior descending coronary artery preconstricted with serotonin. Main Outcome Measures.  Erectile function was assessed as the ICP response to electrical field stimulation (EFS), normalized to MAP. Coronary artery endothelial function was assessed as the effective concentration producing 50% of a maximal response (EC50 ) of the ACh response. Results.  The ICP/MAP response to EFS was significantly attenuated following both 8 and 12 weeks of the WD compared with the control diet (P < 0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P < 0.05). The coronary artery EC50 of the ACh response was not different from control following 4 or 8 weeks but was significantly elevated following 12 weeks of the WD (P < 0.01). Conclusions.  These data suggest that erectile function is reduced prior to coronary artery endothelial function in response to the WD. Improvement of erectile function with sepiapterin in WD rats indicates that nitric oxide

  13. Effects of age and sex on cerebrovascular function in the rat middle cerebral artery

    PubMed Central

    2014-01-01

    Background Although the mechanisms underlying the beneficial effects of estrogen on cerebrovascular function are well known, the age-dependent deleterious effects of estrogen are largely unstudied. It was hypothesized that age and sex interact in modulating cerebrovascular reactivity to vasopressin (VP) by altering the role of prostanoids in vascular function. Methods Female (F) Sprague–Dawley rats approximating key stages of “hormonal aging” in humans were studied: premenopausal (mature multigravid, MA, cyclic, 5–6 months) and postmenopausal (reproductively senescent, RS, acyclic, 10–12 months). Age-matched male (M) rats were also studied. Reactivity to VP (10−12–10−7 M) was measured in pressurized middle cerebral artery segments in the absence or presence of selective inhibitors of COX-1 (SC560, SC, 1 μM) or COX-2 (NS398, NS, 10 μM). VP-stimulated release of PGI2 and TXA2 were measured using radioimmunoassay of 6-keto-PGF1α and TXB2 (stable metabolites, pg/mg dry wt/45 min). Results In M, there were no changes in VP-induced vasoconstriction with age. Further, there were no significant differences in basal or in low- or high-VP-stimulated PGI2 or TXA2 production in younger or older M. In contrast, there were marked differences in cerebrovascular reactivity and prostanoid release with advancing age in F. Older RS F exhibited reduced maximal constrictor responses to VP, which can be attributed to enhanced COX-1 derived dilator prostanoids. VP-induced vasoconstriction in younger MA F utilized both COX-1 and COX-2 derived constrictor prostanoids. Further, VP-stimulated PGI2 and TXA2 production was enhanced by endogenous estrogen and decreased with advancing age in F, but not in M rats. Conclusions This is the first study to examine the effects of age and sex on the mechanisms underlying cerebrovascular reactivity to VP. Interestingly, VP-mediated constriction was reduced by age in F, but was unchanged in M rats. Additionally, it was observed

  14. Dopamine microinjected into brainstem of awake rats affects baseline arterial pressure but not chemoreflex responses.

    PubMed

    Oliva, Waldyr M; Granjeiro, Erica M; Bongamba, Leni G H; Mendes, Ricardo A; Machado, Benedito H

    2010-06-24

    Dopamine (DA) is a neuromodulator in the brainstem involved with the generation and modulation of the autonomic and respiratory activities. Here we evaluated the effect of microinjection of DA intracisterna magna (icm) or into the caudal nucleus tractus solitarii (cNTS) on the baseline cardiovascular and respiratory parameters and on the cardiovascular and respiratory responses to chemoreflex activation in awake rats. Guide cannulas were implanted in cisterna magna or cNTS and femoral artery and vein were catheterized. Respiratory frequency (f(R)) was measured by whole-body plethysmography. Chemoreflex was activated with KCN (iv) before and after microinjection of DA icm or into the cNTS bilaterally while mean arterial pressure (MAP), heart rate (HR) and f(R) were recorded. Microinjection of DA icm (n=13), but not into the cNTS (n=8) produced a significant decrease in baseline MAP (-15+/-1 vs 1+/-1mmHg) and HR (-55+/-11 vs -11+/-17bpm) in relation to control (saline with ascorbic acid, n=9) but no significant changes in baseline f(R). Microinjection of DA icm or into the cNTS produced no significant changes in the pressor, bradycardic and tachypneic responses to chemoreflex activation. These data show that a) DA icm affects baseline cardiovascular regulation, but not baseline f(R) and autonomic and respiratory components of chemoreflex and b) DA into the cNTS does not affect either the autonomic activity to the cardiovascular system or the autonomic and respiratory responses of chemoreflex activation.

  15. The Impact of Different Amounts of Calcium Intake on Bone Mass and Arterial Calcification in Ovariectomized Rats.

    PubMed

    Agata, Umon; Park, Jong-Hoon; Hattori, Satoshi; Aikawa, Yuki; Kakutani, Yuya; Ezawa, Ikuko; Akimoto, Takayuki; Omi, Naomi

    2015-01-01

    Reduced estrogen secretion and low calcium (Ca) intake are risk factors for bone loss and arterial calcification in female rodents. To evaluate the effects of Ca intake at different amounts on bone mass changes and arterial calcification, 8-wk-old female Wistar rats were randomly placed in ovariectomized (OVX) control and OVX with vitamin D3 plus nicotine (VDN) treatment groups. The OVX with VDN rats were then divided into six groups to receive different amounts of Ca in their diets: 0.01%, 0.1%, 0.3%, 0.6%, 1.2%, or 2.4% Ca. After 8 wk of administration, low Ca intake groups with 0.01% and 0.1% Ca diets had significantly reduced bone mineral density (BMD) and bone mechanical properties as compared with those of the other groups, whereas high Ca intake groups with 1.2% and 2.4% Ca diets showed no differences as compared with the 0.6% Ca intake group. For both the 0.01% and 2.4% Ca intake groups, Ca levels in their thoracic arteries were significantly higher as compared with those of the 0.6% Ca diet group, and that was highly correlated with serum PTH levels. An increase in relative BMP-2 mRNA expression in the arterial tissues of the 0.01% and 2.4% Ca diet groups was also observed. These results suggested that extremely low Ca intake during periods of estrogen deficiency may be a possible risk for the complications of reduced BMD and arterial calcification and that extremely high Ca intake may promote arterial calcification with no changes in BMD.

  16. In vivo observation of the hypo-echoic "black hole" phenomenon in rat arterial bloodstream: a preliminary Study.

    PubMed

    Nam, Kweon-Ho; Paeng, Dong-Guk

    2014-07-01

    The "black hole," a hypo-echoic hole at the center of the bloodstream surrounded by a hyper-echoic zone in cross-sectional views, has been observed in ultrasound backscattering measurements of blood with red blood cell aggregation in in vitro studies. We investigated whether the phenomenon occurs in the in vivo arterial bloodstream of rats using a high-frequency ultrasound imaging system. Longitudinal and cross-sectional ultrasound images of the rat common carotid artery (CCA) and abdominal aorta were obtained using a 40-MHz ultrasound system. A high-frame-rate retrospective imaging mode was employed to precisely examine the dynamic changes in blood echogenicity in the arteries. When the imaging was performed with non-invasive scanning, blood echogenicity was very low in the CCA as compared with the surrounding tissues, exhibiting no hypo-echoic zone at the center of the vessel. Invasive imaging of the CCA by incising the skin and subcutaneous tissues at the imaging area provided clearer and brighter blood echo images, showing the "black hole" phenomenon near the center of the vessel in longitudinal view. The "black hole" was also observed in the abdominal aorta under direct imaging after laparotomy. The aortic "black hole" was clearly observed in both longitudinal and cross-sectional views. Although the "black hole" was always observed near the center of the arteries during the diastolic phase, it dissipated or was off-center along with the asymmetric arterial wall dilation at systole. In conclusion, we report the first in vivo observation of the hypo-echoic "black hole" caused by the radial variation of red blood cell aggregation in arterial bloodstream.

  17. Tunicamycin-Induced Alterations in the Vasorelaxant Response in Organ-Cultured Superior Mesenteric Arteries of Rats.

    PubMed

    Matsumoto, Takayuki; Ando, Makoto; Watanabe, Shun; Iguchi, Maika; Nagata, Mako; Kobayashi, Shota; Taguchi, Kumiko; Kobayashi, Tsuneo

    2016-01-01

    In cellular events, endoplasmic reticulum (ER) stress has an important role in the development of various diseases including cardiovascular diseases. Tunicamycin, an inhibitor of N-linked glycosylation, is known to be an inducer of ER stress. However, the extent to which tunicamycin affects the vasorelaxant function is not completely understood. Thus, we investigated the effect of tunicamycin on relaxations induced by various vasorelaxant agents, including acetylcholine (ACh; endothelium-dependent vasodilator), sodium nitroprusside (SNP; endothelium-independent vasodilator), isoprenaline (ISO; beta-adrenoceptor agonist), forskolin (FSK; adenylyl cyclase activator), and cromakalim [ATP-sensitive K(+) (KATP) channel activator] in organ-cultured superior mesenteric arteries of rats, which are treated with either a vehicle [dimethyl sulfoxide (DMSO)] or tunicamycin (20 µg/mL for 22-24 h). Protein levels of the ER stress marker binding immunoglobulin protein (BiP) were determined by Western blotting. Tunicamycin increased the expression of BiP in organ-cultured arteries. Tunicamycin impaired ACh-induced relaxation, but did not alter SNP-induced relaxation. Tunicamycin also impaired vasorelaxation induced by ISO, FSK, and cromakalim; moreover, it reduced basal nitric oxide (NO) formation. In conclusion, short-term treatment with tunicamycin not only caused endothelial dysfunction but also impaired cAMP- and KATP-mediated responses in the superior mesenteric arteries of rats. These alterations in tunicamycin-treated arteries may be due to reduced basal NO formation. This work provides new insight into ER stress in vascular dysfunction. PMID:27582328

  18. Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.

    2000-04-01

    We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

  19. Vasodilator actions of abnormal-cannabidiol in rat isolated small mesenteric artery.

    PubMed

    Ho, W-S Vanessa; Hiley, C Robin

    2003-04-01

    1. The nonpsychoactive cannabinoid abnormal-cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol) (abn-cbd) produced concentration-dependent relaxation of methoxamine-precontracted rat small mesenteric artery. Endothelial removal reduced abn-cbd potency six-fold without affecting the maximum relaxation. 2. In endothelium-intact vessels, abn-cbd was less potent under 60 mM KCl-induced tone and inhibited by combination of L-N(G)-nitroarginine methyl ester (L-NAME) (nitric oxide synthase inhibitor; 300 micro M), apamin (small conductance Ca(2+)-activated K(+) channels inhibitor; 50 nM) and charybdotoxin (inhibitor of intermediate conductance Ca(2+)-activated K(+) channels and large conductance Ca(2+)-activated K(+) channels BK(Ca); 50 nM). L-NAME alone or in combination with either toxin alone had little effect. 3. In intact vessels, relaxations to abn-cbd were inhibited by SR 141716A (cannabinoid receptor antagonist; 1 or 3 micro M). Concomitant addition of L-NAME, apamin and charybdotoxin had no further effect. Other cannabinoid receptor antagonists either had little (SR 144528; 1 micro M and AM 251; 1 micro M) or no effect (AM 630; 10 micro M and AM 281; 1 micro M). Inhibition of gap junctions, G(i/o) protein coupling and protein kinase A also had no effect. 4. Endothelium-independent relaxation to abn-cbd was unaffected by L-NAME, apamin plus charybdotoxin or capsaicin (10 micro M). Abn-cbd inhibited CaCl(2)-induced contractions in vessels with depleted intracellular Ca(2+) stores and stimulated with methoxamine or KCl. This was insensitive to SR 141716A (3 micro M) but greatly reduced in vessels stimulated with ionomycin (Ca(2+) ionophore; 1 micro M). 5. We conclude that abn-cbd relaxes the rat small mesenteric artery by endothelium-dependent activation of K(+) channels via SR 141716A-sensitive pathways, which do not involve CB(1) and CB(2) receptors. It also causes endothelium-independent, SR 141716A

  20. High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats.

    PubMed

    Moreira, M C S; da Silva, E F; Silveira, L L; de Paiva, Y B; de Castro, C H; Freiria-Oliveira, A H; Rosa, D A; Ferreira, P M; Xavier, C H; Colombari, E; Pedrino, Gustavo R

    2014-12-28

    Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0.3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98.6 (sem 2.6) v. 118.3 (sem 2.7) mmHg, P< 0.05) and HR (365.4 (sem 12.2) v. 398.2 (sem 7.5) beats per min, P< 0.05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12.1 (sem 0.6) ml and 7.8 (sem 1.1), respectively, P< 0.05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.

  1. Acetylcholine-induced K+ currents in smooth muscle cells of intact rat small arteries.

    PubMed Central

    Weidelt, T; Boldt, W; Markwardt, F

    1997-01-01

    1. The mechanism of the sustained acetylcholine-induced endothelium-dependent hyperpolarization (EDH) in intact rat small mesenteric arteries prestimulated with noradrenaline (10(-6) M) was investigated by means of the single microelectrode voltage-clamp method. 2. The vascular smooth muscle cells (VSMCs) in this preparation are poorly or even not coupled for the reasons that: (1) the mean input resistance Rlnp of the clamped vascular smooth muscle increases from 120 M omega under control conditions to 440 M omega after application of K+ channel blocking drugs, (2) the voltage relaxation after injection of hyperpolarizing currents has a monoexponential time course and is linearly dependent on Rlnp, and (3) voltage steps induced by current-clamp steps are not transferred to locations in the vascular musculature 120 microns apart from the current injecting microelectrode. 3. Sustained (> 5 min) application of ACh (10(-5) M) hyperpolarized the VSMCs by induction of a hyperpolarizing current. This effect was completely blocked by the inhibitor of the nitric oxide (NO) synthase L-NAME (10(-3) M) but not by the inhibitor of the soluble guanylate cyclase (sGCl) Methylene Blue (MB, 10(-4) M). 4. Application of the NO donor sodium nitroprusside (SNP, 10(-6) M) for more than 5 min mimicked the induction of the endothelium-dependent hyperpolarizing current in vessels with destroyed endothelium. The reversal potential of this current is dependent on the extracellular K+ concentration. The effect of SNP could also not be blocked by MB. 5. The blockers of ATP-dependent and Ca(2+)-dependent K+ channels, glibenclamide (Glb, 10(-5) M) and charybdotoxin (CTX, 5 x 10(-8) M), respectively, blocked a hyperpolarizing current in the VSMCs similar to the ACh- or SNP-induced current. 6. The isolated application of either Glb or CTX did not block the activation of the hyperpolarizing current by SNP. Only the combined administration of Glb and CTX blocked the SNP-induced current completely

  2. Nitric oxide decreases stability of mRNAs encoding soluble guanylate cyclase subunits in rat pulmonary artery smooth muscle cells.

    PubMed Central

    Filippov, G; Bloch, D B; Bloch, K D

    1997-01-01

    Nitric oxide stimulates soluble guanylate cyclase (sGC) to convert GTP to the intracellular second messenger cGMP. In rat pulmonary artery smooth muscle cells, sGC is an obligate heterodimer composed of alpha1 and beta1 subunits. We investigated the effect of NO donor compounds on sGC subunit gene expression in rat pulmonary artery smooth muscle cells. Sodium nitroprusside and S-nitroso-glutathione decreased sGC subunit mRNA and protein levels, as well as sGC enzyme activity. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor, blocked the effect of sodium nitroprusside on sGC subunit gene expression, whereas 8-bromo cGMP decreased subunit mRNA levels, demonstrating that NO-mediated decrease in sGC subunit mRNA levels is cGMP-dependent. sGC subunit mRNA levels decreased more rapidly in rat pulmonary artery smooth muscle cells exposed to NO than in cells exposed to actinomycin D, suggesting that NO decreases sGC subunit mRNA stability. Actinomycin D and cycloheximide blocked the ability of NO to decrease sGC subunit mRNA levels. These results demonstrate that NO decreases sGC subunit mRNA stability via a transcription- and translation-dependent mechanism. PMID:9259594

  3. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion

    PubMed Central

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2015-01-01

    Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia. PMID:26441669

  4. Adipose-derived stromal cell autologous transplantation ameliorates pulmonary arterial hypertension induced by shunt flow in rat models.

    PubMed

    Liu, Kai; Liu, Ruifang; Cao, Guangqing; Sun, Hourong; Wang, Xuping; Wu, Shuming

    2011-06-01

    Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured, and labeled in vitro. Twelve weeks after shunt operation, rats received an injection of 5 × 10(7) ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, which was confirmed by invasive measurement and echocardiography examination. The PAH rats receiving cell transplantation demonstrated decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed augmented expression of hepatocyte growth factor (HGF) and increased number of pulmonary small arteries. Western blot and real-time reverse transcriptase-polymerase chain reaction indicated that the protein and mRNA levels of HGF and endothelial nitric oxide synthase increased, respectively, in the lung after cell transplantation. Our results suggested that ADSC transplantation can ameliorate PAH induced by shunt flow by enhancing the expression of HGF and subsequently promoting angiogenesis in the injured lung tissue. PMID:20828291

  5. Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography

    PubMed Central

    Buyukakilli, Belgin; Gurgul, Serkan; Cıtırık, Derya; Hallioglu, Olgu; Ozeren, Murat; Tasdelen, Bahar

    2014-01-01

    Aim To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks. Results Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups. Conclusion PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index. PMID:25358882

  6. The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery.

    PubMed

    Bopp, Claire; Auger, Cyril; Diemunsch, Pierre; Schini-Kerth, Valérie

    2016-05-15

    Urapidil (Eupressyl(®)) an antihypertensive drug acting as an α1 antagonist and a 5-HT1A agonist, may be of special interest in the treatment of hypertension associated with preeclamptic toxaemia and hypoxia-induced pulmonary arterial vasoconstriction. However, the effect of urapidil on vascular tone has been poorly investigated. Vascular reactivity was evaluated using pulmonary and coronary arteries from 36 pigs, aortae from 22 rats and 9 human pulmonary artery samples suspended in organ chambers. Concentration-relaxation curves either to urapidil, 5-HT, or the 5-HT1A receptor agonist 8-OH-DPAT were constructed after pre-contraction of rings. Pig pulmonary and coronary artery rings were contracted with U46619, a thromboxane mimetic, rat aortic rings with either endothelin-1 or phenylephrine, and human pulmonary artery rings with U46619 or phenylephrine. Urapidil markedly inhibited phenylephrine-induced contractions in rat aortic rings with and without endothelium with a more pronounced effect observed in rings without endothelium. Both 5-HT and 8-OH-DPAT failed to induce relaxation in rat aortic rings with an intact endothelium. 5-HT, but not urapidil and 8-OH-DPAT, induced a concentration-dependent relaxation in the porcine coronary and pulmonary artery rings with an intact endothelium (P<0.05). 5-HT and phenylephrine but not urapidil caused concentration-dependent contractions in human pulmonary artery rings. The present findings, while confirming that urapidil is a potent inhibitor of α1-adrenoceptor-induced contraction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone of the different types of arteries tested in response to urapidil. In addition, they indicate that urapidil seems to preferentially target arteries with endothelial dysfunction.

  7. Effects of basilar membrane arch and radial tension on the travelling wave in gerbil cochlea.

    PubMed

    Chan, Wei Xuan; Yoon, Yong-Jin

    2015-09-01

    The basilar membrane velocity of gerbil cochlea showed discrepancy between theoretical model and experimental measurements. We hypothesize that the reasons of such discrepancies are due to the arch towards the scala tympani and radial tension present in the basilar membrane of the gerbil cochlea. The arch changes the bending stiffness in the basilar membrane, reduces the effective fluid force on the membrane and increases the basilar membrane's inertia. The existence of the radial tension also dampens the acoustic travelling wave. In this paper, the wave number functions along the gerbil basilar membrane are calculated from experimentally measured physical parameters with the theoretical model as well as extracted from experimentally measured basilar membrane velocity with the wave number inversion formula. The two wave number functions are compared and the effects of the tension and membrane arch on the wave number are studied based on various parameters of the model. We found that the bending stiffness across the gerbil basilar membrane varies (1-2 orders along the cochlea in the section 2.2 mm-3 mm from base) more than the calculated value in the flat basilar membrane model and the radial tension increases the damping of the travelling wave in gerbil cochlea significantly (5 times more than that without radial tension). These effects of arch and radial tension in the basilar membrane elucidate the discrepancy between previous theoretical model and experimental measurements in gerbil cochlea.

  8. Vascular Microanatomy of the Pontomedullary Junction, Posterior Inferior Cerebellar Arteries, and the Lateral Spinal Arteries

    PubMed Central

    Mercier, PH.; Brassier, G.; Fournier, H-D; Picquet, J.; Papon, X.; Lasjaunias, P.

    2008-01-01

    Summary This study of 25 brains at the pontomedullary junction defined the different possible origins of the perforating arteries and lateral spinal arteries in relation to the posterior inferior cerebellar arteries (PICAs). - If the PICA emerges from the common trunk of the AICA-PICA coming from the basilar artery, it never gives perforating arteries or a lateral spinal artery on the lateral surface of the brain stem but supplies blood to a part of the ipsilateral cerebellar hemisphere. - If the PICA arises extradurally at C1, it never gives perforating arteries for the lateral surface of the brain stem, but it gives pial branches for the posterior surface of the medulla oblongata and is always the origin of the lateral spinal artery. - If the PICA emerges in the intradural vertebral artery, it is the source of the perforating arteries for the lateral surface of the brain stem and of the blood supply of the ipsilateral cerebellum. PMID:20557786

  9. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    SciTech Connect

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-02-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--/sup 14/C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

  10. Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

    PubMed Central

    Irwin, David C.; Garat, Chrystelle V.; Crossno, Joseph T.; MacLean, Paul S.; Sullivan, Timothy M.; Erickson, Paul F.; Jackman, Matthew R.; Harral, Julie W.; Reusch, Jane E. B.

    2014-01-01

    Abstract Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia. PMID:25610600

  11. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries.

  12. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries. PMID:26671004

  13. Vertebral artery stenting by using coronary intervention techniques and devices.

    PubMed

    Kilic, Harun; Balci, Mustafa; Akdemir, Ramazan

    2009-04-01

    Atherosclerotic disease of the vertebro/basilar vessels is an important cause of posterior circulation infarction. Commonly, the primary atheroma forms at the origin of the vertebral arteries. Although initial treatment is medical, arch and four-vessel studies (CTA, MRA, or DSA) are warranted if symptoms continue. Endovascular management of vertebral artery stenosis might be highlighted as a good option in selected patients. This is a case of endoluminal stenting of vertebral artery with a durable result. PMID:19476126

  14. Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

    PubMed Central

    Ma, Jianhua; Zhang, Maoying; Li, Shaowu; Wu, Bingshan; Nie, Xiaohu; Jiao, Jiao; Zhao, Hao; Wang, Shanshan; Yang, Yuanyuan; Zhang, Yesen; Sun, Yilin; Wicha, Max S.; Chang, Alfred E.; Gao, Shaorong; Li, Qiao; Xu, Ruxiang

    2015-01-01

    Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells. PMID:26352672

  15. Garcinielliptone FC, a polyisoprenylated benzophenone from Platonia insignis Mart., promotes vasorelaxant effect on rat mesenteric artery.

    PubMed

    Arcanjo, Daniel Dias Rufino; da Costa-Júnior, Joaquim Soares; Moura, Lucas Henrique Porfírio; Ferraz, Alexandre Barros Falcão; Rossatto, Raíssa Rebés; David, Jorge Maurício; Quintans-Júnior, Lucindo José; Oliveira, Rita de Cássia Meneses; Citó, Antônia Maria das Graças Lopes; de Oliveira, Aldeídia Pereira

    2014-01-01

    Polyisoprenylated benzophenones represent a group of chemical compounds commonly identified in Clusiaceae species and are responsible for a large amount of biological activities. In this work, the vasorelaxant effect induced by garcinielliptone FC (GFC) isolated from Platonia insignis Mart. (Clusiaceae), a monotype species from Platonia genus, was investigated. GFC promoted an endothelium-independent vasorelaxation on phenylephrine (PHE, 10(-5) mol L(-1))-induced vasoconstriction, but not on KCl (80 mmol L(-1))-induced vasoconstriction, on rat superior mesenteric artery rings. In addition, a concentration-dependent decrease of PHE- or serotonin-induced cumulative concentration-response curves was observed for GFC, and a slight decrease of pD₂ value on CaCl₂-induced vasoconstriction. In a Ca(2+)-free medium, GFC interfered in calcium mobilisation from PHE (10(-5) mol L(-1))-sensitive intracellular stores. GFC-induced vasorelaxant effect is probably mediated by a dual effect on mobilisation of calcium intracellular stores and attenuation of transmembrane calcium influx. PMID:24579922

  16. Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats.

    PubMed

    Martz, D; Rayos, G; Schielke, G P; Betz, A L

    1989-04-01

    Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals.

  17. [Study on targeting drug delivery system--the characteristics of methotrexate microsphere and experimental treatment of hepatic tumor in rats by arterial embolization].

    PubMed

    Chen, Q H; Lu, W G; Ge, Q H; Sheng, Q; Zhang, Y; Xie, X H; Wang, Y; Wu, M C; Zhang, X H

    1991-01-01

    Preparation of methotrexate microsphere (MTX-ms) by emulsion-freezing technique was introduced and the experimental results proved that MTX entrapped in the microspheres exhibited good stabilities towards temperature, cobalt-60 radiation and light. The dissolution and inflation rate of the microspheres in pH 7.4 buffer solution at different times measured by Coulter counter was presented. Antitumor activity of MTX-ms after hepatic arterial embolization was examined in a model of liver tumor in Wistar rats. The group of rats treated with MTX-ms showed a rather significant reduction in tumor growth and more extended tumor necrosis as compared with the other groups, e.g. normal saline solution, MTX solution, placebo gelatin-ms and the results demonstrate that the effect of arterial chemoembolization used by MTX-ms is superior to that of the groups either using arterial chemotherapy or arterial embolization alone in treating rat liver cancer.

  18. Biphasic Effect of Diabetes on Neuronal Nitric Oxide Release in Rat Mesenteric Arteries

    PubMed Central

    Sastre, Esther; Caracuel, Laura; Blanco-Rivero, Javier; Callejo, María; Xavier, Fabiano E.; Balfagón, Gloria

    2016-01-01

    Introduction We analysed possible time-dependent changes in nitrergic perivascular innervation function from diabetic rats and mechanisms implicated. Materials and Methods In endothelium-denuded mesenteric arteries from control and four- (4W) and eight-week (8W) streptozotocin-induced diabetic rats the vasoconstriction to EFS (electrical field stimulation) was analysed before and after preincubation with L-NAME. Neuronal NO release was analysed in the absence and presence of L-arginine, tetrahydrobiopterine (BH4) and L-arginine plus BH4. Superoxide anion (O2-), peroxynitrite (ONOO-) and superoxide dismutase (SOD) activity were measured. Expressions of Cu-Zn SOD, nNOS, p-nNOS Ser1417, p-nNOS Ser847, and Arginase (Arg) I and II were analysed. Results EFS response was enhanced at 4W, and to a lesser extent at 8W. L-NAME increased EFS response in control rats and at 8W, but not at 4W. NO release was decreased at 4W and restored at 8W. L-arginine or BH4 increased NO release at 4W, but not 8W. SOD activity and O2- generation were increased at both 4W and 8W. ONOO- decreased at 4W while increased at 8W. Cu-Zn SOD, nNOS and p-NOS Ser1417 expressions remained unmodified at 4W and 8W, whereas p-nNOS Ser847 was increased at 4W. ArgI was overexpressed at 4W, remaining unmodified at 8W. ArgII expression was similar in all groups. Conclusions Our results show a time-dependent effect of diabetes on neuronal NO release. At 4W, diabetes induced increased O2- generation, nNOS uncoupling and overexpression of ArgI and p-nNOS Ser847, resulting in decreased NO release. At 8W, NO release was restored, involving normalisation of ArgI and p-nNOS Ser847 expressions. PMID:27272874

  19. Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries.

    PubMed

    Hedegaard, Elise R; Gouliaev, Anja; Winther, Anna K; Arcanjo, Daniel D R; Aalling, Mathilde; Renaltan, Nirthika S; Wood, Mark E; Whiteman, Matthew; Skovgaard, Nini; Simonsen, Ulf

    2016-01-01

    Endogenous hydrogen sulfide (H2S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calcium-independent mechanisms are involved in H2S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H2S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na2S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H2S], GYY4137 caused more relaxation in relation to released free H2S than NaHS and Na2S in rat mesenteric small arteries. Simultaneous measurements of [H2S] and tension showed that 15 µM of free H2S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated KV7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H2S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation. PMID:26493746

  20. Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries.

    PubMed

    Hedegaard, Elise R; Gouliaev, Anja; Winther, Anna K; Arcanjo, Daniel D R; Aalling, Mathilde; Renaltan, Nirthika S; Wood, Mark E; Whiteman, Matthew; Skovgaard, Nini; Simonsen, Ulf

    2016-01-01

    Endogenous hydrogen sulfide (H2S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calcium-independent mechanisms are involved in H2S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H2S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na2S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H2S], GYY4137 caused more relaxation in relation to released free H2S than NaHS and Na2S in rat mesenteric small arteries. Simultaneous measurements of [H2S] and tension showed that 15 µM of free H2S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated KV7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H2S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation.

  1. Persistent Primitive Trigeminal Artery That Mimics Persistent Primitive Otic Artery on Cerebral Angiography

    PubMed Central

    Lee, Kwangho; Park, Insung; Han, Jongwoo

    2016-01-01

    Persistent primitive trigeminal artery (PPTA) is the most common carotid-basilar anastomosis; on the other hand, persistent primitive otic artery (PPOA) is extremely rare. PPTA is often misdiagnosed as PPOA on cerebral angiography. We present a case of PPTA that mimicked PPOA on cerebral angiography. We further describe the utility of brain computed tomography angiography for differential diagnosis of PPTA from PPOA, together with a review of previous literature. PMID:27790403

  2. Breast Feeding Increases Vasoconstriction Induced by Electrical Field Stimulation in Rat Mesenteric Artery. Role of Neuronal Nitric Oxide and ATP

    PubMed Central

    Caracuel, Laura; Granado, Miriam; Balfagón, Gloria

    2013-01-01

    Objectives The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF) affects the vasomotor response induced by electrical field stimulation (EFS), participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. Methods Experiments were performed in female Sprague-Dawley rats (3 months old), divided into three groups: Control (in oestrous phase), mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase). Vasomotor response to EFS, noradrenaline (NA) and nitric oxide (NO) donor DEA-NO were studied. Neuronal NO synthase (nNOS) and phosphorylated nNOS (P-nNOS) protein expression were analysed and NO, superoxide anion (O2.–), NA and ATP releases were also determined. Results EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O2.– production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. Conclusion Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats. PMID:23342008

  3. Ischemia as a potential etiologic factor in idiopathic unilateral sudden sensorineural hearing loss: Analysis of posterior circulation arteries.

    PubMed

    Kim, Chulho; Sohn, Jong-Hee; Jang, Min Uk; Hong, Sung-Kwang; Lee, Joong-Seob; Kim, Hyung-Jong; Choi, Hui-Chul; Lee, Jun Ho

    2016-01-01

    The association between idiopathic sudden sensorineural hearing loss (ISSNHL) and the radiologic characteristics of the vertebrobasilar artery is unclear. We hypothesized that the degree and direction of vertebrobasilar artery curvature in the posterior circulation contribute to the occurrence of ISSNHL. We consecutively enrolled patients diagnosed with unilateral ISSNHL in two tertiary hospitals. Magnetic resonance images were performed in all patients to exclude specific causes of ISSNHL, such as vestibular schwannoma, chronic mastoiditis, and anterior inferior cerebellar artery infarct. We measured the following parameters of posterior circulation: vertebral and basilar artery diameter, the degree of basilar artery curvature (modified smoker criteria), and vertebral artery dominance. Pure tone audiometries were performed at admission and again 1 week and 3 months later. A total of 121 ISSNHL patients (mean age, 46.0 ± 17.3 years; 48.8% male) were included in these analyses. The proportion of patients with the left side hearing loss was larger than the proportion with the right side hearing loss (left, 57.9%; right, 42.1%). The majority of patients were characterized by a left dominant vertebral artery and right-sided basilar artery curvature. The direction of the basilar artery curvature was significantly associated with hearing loss lateralization (p = 0.036). Age and sex matched multivariable analyses revealed the absence of diabetes and right-sided basilar artery curvature as significant predictors for left sided hearing loss. There was no statistical difference between atherosclerotic cardiovascular risk score (high versus low) and hearing outcomes at 3 months. In ISSNHL, the laterality of hearing loss was inversely associated with the direction of basilar artery curvature. Our results, therefore, indicate the importance of vascular assessment when evaluating ISSNHL.

  4. Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

    PubMed

    Chang, K C; Su, M J; Peng, Y I; Shao, C C; Wu, Y C; Tseng, Y Z

    2001-05-01

    1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats. 2. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E(es)) and effective arterial volume elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(-7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system. PMID:11325791

  5. Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats

    PubMed Central

    Shanbhag, Nagesh C.; Henning, Robert H.; Schilling, Lothar

    2016-01-01

    Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients. PMID:27329690

  6. Simple and choice reaction-time performance following occlusion of the anterior cerebral arteries in the rat.

    PubMed

    Ward, N M; Sharkey, J; Marston, H M; Brown, V J

    1998-12-01

    Focal cerebral ischemia in the rat has traditionally been studied by examining the consequences of middle-cerebral artery occlusion. However, the anteriorcerebral arteries of the rat may now also be bilaterally occluded by stereotaxic injection of the vasoconstrictor endothelin-1, resulting in ischemic damage to medial prefrontal cortex and the anteromedial basal forebrain. The behavioural consequences of anterior-cerebral artery occlusion (ACAo) were studied in two experiments using simple and choice reaction-time tasks designed to dissociate response impairments from dysfunction of motivation and attention, respectively. Following ACAo, reaction-time increased post-surgery in the choice, but not simple reaction-time task. There was also an increase in incorrect choices in the choice reaction-time task. However, the impairments were independent of motivational or attentional function, which remained intact. Although the ACAo-induced ischemic damage did not disrupt motivation or attention, the results suggest that the lesion results in an executive impairment in selecting and initiating responses.

  7. Beta-adrenoceptor agonist mediated relaxation of rat isolated resistance arteries: a role for the endothelium and nitric oxide.

    PubMed Central

    Graves, J.; Poston, L.

    1993-01-01

    1. Isoprenaline (10(-9)-10(-5) M) relaxed rat isolated mesenteric resistance arteries pre-contracted with K+ (30-60 mM) (p EC50 (M) 8.03 +/- 0.40; maximum relaxation 66.79 +/- 2.43%, n = 7). This relaxation was partially attenuated by the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). 2. The beta 2-adrenoceptor agonist, salbutamol (10(-9)-10(-5) M), produced a modest maximum relaxation (35.93 +/- 2.93%), which was not sensitive to L-NAME. 3. The beta 1-adrenoceptor agonist, dobutamine (10(-9)-10(-5) M), relaxed arteries precontracted with K+. This relaxation was abolished by L-NAME (10(-4) M) and also by propranolol (10(-6) M), but not affected by D-NAME (10(-4) M). The inhibition by L-NAME was partially reversed by L-arginine (10(-3) M). Removal of the endothelium severely attenuated relaxation to dobutamine. 4. Contractile responses to depolarizing K+ solutions were enhanced by the addition of L-NAME, and also by removal of the endothelium. 5. The above findings demonstrate that beta 1-adrenoceptor causes relaxation via NO release from the endothelium of rat mesenteric resistance arteries. In addition, contraction to K+ is modified by release of NO from the endothelium, possibly in response to tension development. PMID:8096781

  8. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    PubMed

    Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Arribas, Silvia M; González, Maria Carmen; Fresco, Paula; Diniz, Carmen

    2015-01-01

    Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

  9. Diminished Neurogenic Femoral Artery Vasoconstrictor Response in a Zucker Obese Rat Model: Differential Regulation of NOS and COX Derivatives

    PubMed Central

    Martínez, Ana Cristina; Hernández, Medardo; Novella, Susana; Martínez, María Pilar; Pagán, Rosa María; Hermenegildo, Carlos; García-Sacristán, Albino; Prieto, Dolores; Benedito, Sara

    2014-01-01

    Objective Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. Conclusions Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation. PMID:25216050

  10. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

    PubMed Central

    Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Arribas, Silvia M.; González, Maria Carmen; Fresco, Paula; Diniz, Carmen

    2015-01-01

    Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation. PMID:26075386

  11. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    PubMed

    Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Arribas, Silvia M; González, Maria Carmen; Fresco, Paula; Diniz, Carmen

    2015-01-01

    Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation. PMID:26075386

  12. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  13. Functional Expression Profile of Voltage-Gated K(+) Channel Subunits in Rat Small Mesenteric Arteries.

    PubMed

    Cox, Robert H; Fromme, Samantha

    2016-06-01

    Multiple K v channel complexes contribute to total K v current in numerous cell types and usually subserve different physiological functions. Identifying the complete compliment of functional K v channel subunits in cells is a prerequisite to understanding regulatory function. It was the goal of this work to determine the complete K v subunit compliment that contribute to functional K v currents in rat small mesenteric artery (SMA) myocytes as a prelude to studying channel regulation. Using RNA prepared from freshly dispersed myocytes, high levels of K v 1.2, 1.5, and 2.1 and lower levels of K v 7.4 α-subunit expressions were demonstrated by quantitative PCR and confirmed by Western blotting. Selective inhibitors correolide (K v 1; COR), stromatoxin (K v 2.1; ScTx), and linopirdine (K v 7.4; LINO) decreased K v current at +40 mV in SMA by 46 ± 4, 48 ± 4, and 6.5 ± 2 %, respectively, and K v current in SMA was insensitive to α-dendrotoxin. Contractions of SMA segments pretreated with 100 nmol/L phenylephrine were enhanced by 27 ± 3, 30 ± 8, and 7 ± 3 % of the response to 120 mmol/L KCl by COR, ScTX, and LINO, respectively. The presence of K v 6.1, 9.3, β1.1, and β1.2 was demonstrated by RT-PCR using myocyte RNA with expressions of K vβ1.2 and K v 9.3 about tenfold higher than K vβ1.1 and K v 6.1, respectively. Selective inhibitors of K v 1.3, 3.4, 4.1, and 4.3 channels also found at the RNA and/or protein level had no significant effect on K v current or contraction. These results suggest that K v current in rat SMA myocytes are dominated equally by two major components consisting of K v 1.2-1.5-β1.2 and K v 2.1-9.3 channels along with a smaller contribution from K v 7.4 channels but differences in voltage dependence of activation allows all three to provide significant contributions to SMA function at physiological voltages.

  14. Functional Expression Profile of Voltage-Gated K(+) Channel Subunits in Rat Small Mesenteric Arteries.

    PubMed

    Cox, Robert H; Fromme, Samantha

    2016-06-01

    Multiple K v channel complexes contribute to total K v current in numerous cell types and usually subserve different physiological functions. Identifying the complete compliment of functional K v channel subunits in cells is a prerequisite to understanding regulatory function. It was the goal of this work to determine the complete K v subunit compliment that contribute to functional K v currents in rat small mesenteric artery (SMA) myocytes as a prelude to studying channel regulation. Using RNA prepared from freshly dispersed myocytes, high levels of K v 1.2, 1.5, and 2.1 and lower levels of K v 7.4 α-subunit expressions were demonstrated by quantitative PCR and confirmed by Western blotting. Selective inhibitors correolide (K v 1; COR), stromatoxin (K v 2.1; ScTx), and linopirdine (K v 7.4; LINO) decreased K v current at +40 mV in SMA by 46 ± 4, 48 ± 4, and 6.5 ± 2 %, respectively, and K v current in SMA was insensitive to α-dendrotoxin. Contractions of SMA segments pretreated with 100 nmol/L phenylephrine were enhanced by 27 ± 3, 30 ± 8, and 7 ± 3 % of the response to 120 mmol/L KCl by COR, ScTX, and LINO, respectively. The presence of K v 6.1, 9.3, β1.1, and β1.2 was demonstrated by RT-PCR using myocyte RNA with expressions of K vβ1.2 and K v 9.3 about tenfold higher than K vβ1.1 and K v 6.1, respectively. Selective inhibitors of K v 1.3, 3.4, 4.1, and 4.3 channels also found at the RNA and/or protein level had no significant effect on K v current or contraction. These results suggest that K v current in rat SMA myocytes are dominated equally by two major components consisting of K v 1.2-1.5-β1.2 and K v 2.1-9.3 channels along with a smaller contribution from K v 7.4 channels but differences in voltage dependence of activation allows all three to provide significant contributions to SMA function at physiological voltages. PMID:27286858

  15. Enhanced Endothelin-1 Mediated Vasoconstriction of the Ophthalmic Artery May Exacerbate Retinal Damage after Transient Global Cerebral Ischemia in Rat

    PubMed Central

    Blixt, Frank W.; Johansson, Sara Ellinor; Johnson, Leif; Haanes, Kristian Agmund; Warfvinge, Karin; Edvinsson, Lars

    2016-01-01

    Cerebral vasculature is often the target of stroke studies. However, the vasculature supplying the eye might also be affected by ischemia. The aim of the present study was to investigate if the transient global cerebral ischemia (GCI) enhances vascular effect of endothelin-1 (ET-1) and 5-hydroxytryptamine/serotonin (5-HT) on the ophthalmic artery in rats, leading to delayed retinal damage. This was preformed using myography on the ophthalmic artery, coupled with immunohistochemistry and electroretinogram (ERG) to assess the ischemic consequences on the retina. Results showed a significant increase of ET-1 mediated vasoconstriction at 48 hours post ischemia. The retina did not exhibit any morphological changes throughout the study. However, we found an increase of GFAP and vimentin expression at 72 hours and 7 days after ischemia, indicating Müller cell mediated gliosis. ERG revealed significantly decreased function at 72 hours, but recovered almost completely after 7 days. In conclusion, we propose that the increased contractile response via ET-1 receptors in the ophthalmic artery after 48 hours may elicit negative retinal consequences due to a second ischemic period. This may exacerbate retinal damage after ischemia as illustrated by the decreased retinal function and Müller cell activation. The ophthalmic artery and ET-1 mediated vasoconstriction may be a valid and novel therapeutic target after longer periods of ischemic insults. PMID:27322388

  16. Absence of enhanced intimal thickening in the response of the carotid arterial wall to endothelial injury in hypercholesterolemic rats.

    PubMed

    Clowes, A W; Ryan, G B; Breslow, J L; Karnovsky, M J

    1976-07-01

    Young male Sprague-Dawley rats fed a high cholesterol, thyroid-suppressive diet were subjected to drying injury of carotid artery endothelium; animals were sacrificed at various times up to 3 months after injury, and the vessels were examined by light, scanning, and transmission electron microscopy. The diet induced marked elevation of serum cholesterol mainly present in lipoproteins of density less than 1.063. The morphology and degree of intimal thickening in the injured carotids of such animals were compared with the changes found in control groups of normolipemic rats. In the control groups, endothelium was completely regenerated between 7 and 14 days; intimal thickening was present at 14 days and at later stages and contained smooth muscle cells without lipid. In the cholesterol-fed animals, endothelial regeneration and intimal thickening occurred as in the controls with the following additional features: in the zone of intimal thickening in the injured segment, lipid was present in smooth muscle cells and, at later stages, in the extracellular matrix; undifferentiated mononuclear cells were also noted in the thickened intima and, at 3 months, were found adhering to normal and regenerated endothelium. However, no differences were found between control and hypercholesterolemic rats with respect to the degree of intimal thickening within the injured segment; enhancement of the smooth muscle proliferative response was not evident in the hypercholesterolemic rats. Our findings suggest that this form of hypercholesterolemia and its associated hyperlipoproteinemia may not be directly responsible for rat smooth muscle proliferation following endothelial denudation. They also indicate that hyperlipemia does not necessarily cause persistence of myointimal hyperplasia in arteries.

  17. Reduced liver uptake of arterially infused melphalan during retrograde rat liver perfusion with unaffected liver tumor uptake.

    PubMed

    Rothbarth, Joost; Sparidans, Rolf W; Beijnen, Jos H; Schultze-Kool, Leo J; Putter, Hein; van de Velde, Cornelis J H; Mulder, Gerard J

    2002-11-01

    Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell line. After 11 to 12 days the tumor-bearing rat livers were perfused by single-pass perfusion through either the portal (orthograde) or caval vein (retrograde) for different time periods. During perfusion melphalan (160 Schultze) was infused in the hepatic artery. Melphalan concentrations were measured by high-performance liquid chromatography. A rapid extraction of melphalan by the liver occurred in the first 5 min, reaching steady state after 10 to 20 min for both perfusion directions. The melphalan concentration of the outflow perfusate was significantly higher in the retrograde perfusion compared with the orthograde perfusion. The melphalan content of the tumor tissue was unaffected by perfusion direction at any time point. To the contrary, the melphalan uptake in liver tissue was strongly influenced: the melphalan content after 40-min retrograde perfusion was 12% of that after orthograde perfusion. The average tumor/liver concentration ratio was 6 for orthograde perfusion and 30 for retrograde perfusion. In conclusion, retrograde IHP with continuous melphalan infusion in the hepatic artery provides a high tumor uptake of melphalan with potentially reduced liver toxicity compared with orthograde IHP. PMID:12388659

  18. 1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

    PubMed Central

    Lin, Taijie; Gu, Jinping; Huang, Caihua; Zheng, Suli; Lin, Xu; Xie, Liangdi; Lin, Donghai

    2016-01-01

    Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (n = 8, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles. Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis. Conclusions. Metabolic dysfunction is involved in the development and progression of PAH. PMID:27057080

  19. Acute Neuromuscular Adaptation at the Spinal Level Following Middle Cerebral Artery Occlusion-Reperfusion in the Rat

    PubMed Central

    Pin-Barre, Caroline; Laurin, Jérôme; Felix, Marie-Solenne; Pertici, Vincent; Kober, Frank; Marqueste, Tanguy; Matarazzo, Valery; Muscatelli-Bossy, Françoise; Temprado, Jean-Jacques; Brisswalter, Jeanick; Decherchi, Patrick

    2014-01-01

    The purpose of the study was to highlight the acute motor reflex adaptation and to deepen functional deficits following a middle cerebral artery occlusion-reperfusion (MCAO-r). Thirty-six Sprague-Dawley rats were included in this study. The middle cerebral artery occlusion (MCAO; 120 min) was performed on 16 rats studied at 1 and 7 days, respectively (MCAO-D1 and MCAO-D7, n = 8 for each group). The other animals were divided into 3 groups: SHAM-D1 (n = 6), SHAM-D7 (n = 6) and Control (n = 8). Rats performed 4 behavioral tests (the elevated body swing test, the beam balance test, the ladder-climbing test and the forelimb grip force) before the surgery and daily after MCAO-r. H-reflex on triceps brachii was measured before and after isometric exercise. Infarction size and cerebral edema were respectively assessed by histological (Cresyl violet) and MRI measurements at the same time points than H-reflex recordings. Animals with cerebral ischemia showed persistent functional deficits during the first week post-MCAO-r. H-reflex was not decreased in response to isometric exercise one day after the cerebral ischemia contrary to the other groups. The motor reflex regulation was recovered 7 days post-MCAO-r. This result reflects an acute sensorimotor adaptation at the spinal level after MCAO-r. PMID:24587147

  20. On the secretory activity of single varicosities in the sympathetic nerves innervating the rat tail artery.

    PubMed

    Astrand, P; Stjärne, L

    1989-02-01

    1. Nerve terminal impulses (NTIs) and spontaneous or stimulus-evoked excitatory junction currents (SEJCs or EJCs), reflecting secretion of transmitter quanta from release sites in the sympathetic nerves of rat tail artery, were recorded by extracellular electrodes. 2. The release of transmitter quanta from single varicosities was analysed on a pulse-by-pulse basis. 3. Since the SEJCs were tetrodotoxin-resistant, and hence probably caused by single quanta, they were employed to analyse the quantal content of EJCs. 4. In the majority of recordings, EJCs were large compared to SEJCs from the same attachment, and preceded by prominent NTIs. This type of activity appeared to reflect simultaneous activation of several nerve fibres and numerous varicosities. 5. By focal stimulation, it was usually possible to improve the resolution by examining spots in which a large proportion of the suprathreshold stimuli failed to cause EJCs. Here, averaged NTIs preceding large EJCs were indistinguishable from averaged NTIs not followed by EJCs. Thus, failure of invasion by the nerve impulse was not a cause of the frequent secretory failure. 6. In these attachments the amplitude distribution of nerve stimulus-evoked EJCs was similar to that of the SEJCs and many individual EJCs could be matched in amplitude and time course by SEJCs. Thus, transmitter secretion from these sympathetic nerve varicosities seems to be basically monoquantal. 7. Under conditions when all EJCs were smaller than or equal to the largest SEJCs some characteristic EJC profiles appeared only a few times in response to several hundred suprathreshold stimuli at low frequency (0.5-1 Hz). Using tentatively these EJCs as 'fingerprints' of single quanta from particular release sites, the probability for activation of individual release sites ranges from 0.002 to 0.02.

  1. Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic rats challenged with endotoxin: the role of TLR4.

    PubMed

    Ostadhadi, Sattar; Rezayat, Seyed-Mahdi; Ejtemaei-Mehr, Shahram; Tavangar, Seyed-Mohammad; Nikoui, Vahid; Jazaeri, Farahnaz; Eftekhari, Golnar; Abdollahi, Alireza; Dehpour, Ahmad-Reza

    2015-06-01

    Cirrhosis is associated with vascular dysfunction and endotoxemia. These experiments were designed to investigate the hypothesis that the administration of a low-dose of lipopolysaccharide (LPS) worsens vascular dysfunction in rats subjected to bile-duct ligation (BDL), and to determine whether LPS initiates changes in vascular Toll-like receptor 4 (TLR4) expression. Four weeks after BDL, the animals were given an intraperitoneal injection of either saline or LPS (1.0 mg/kg body mass). Three hours later, the superior mesenteric artery was isolated, perfused, and then subjected to the vasoconstriction and vasodilatation effects of phenylephrine and acetylcholine, respectively. Our results show that phenylephrine-induced vasoconstriction decreased in the cirrhotic vascular bed (BDL rats) compared with the vascular bed of the sham-operated animals, and that the LPS injections in the cirrhotic (BDL) rats worsened this response. LPS injection administered to the sham-operated animals had no such effect. On the other hand, both the BDL procedure and the LPS injection increased acetylcholine-induced vasorelaxation, but LPS administration to the BDL rats had no effect on this response. The mRNA levels of TLR4 did not change, but immunohistochemical studies showed that TLR4 localization switched from the endothelium to vascular smooth muscle cells following chronic BDL. In conclusion, acute endotoxemia in cirrhotic rats is associated with hyporesponsiveness to phenylephrine and tolerance to the effects of acetylcholine. Altered localization of TLR4 may be responsible for these effects.

  2. Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats

    PubMed Central

    2011-01-01

    Background Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke. Methods Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra. Results 24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p < 0.001), TNF-α (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls. Conclusions Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions. PMID:22082476

  3. Hair bundle profiles along the chick basilar papilla

    PubMed Central

    DUNCAN, R. K.; ILE, K. E.; DUBIN, M. G.; SAUNDERS, J. C.

    2001-01-01

    Cochlear hair cells play a central role in the transduction of sound into neural output. Anatomical descriptions of these cells, and their protruding hair bundles, are of fundamental interest since hair cell transduction is dependent on hair bundle micromechanics and hair bundle micromechanics depends on hair bundle morphology. In this paper, we describe quantitatively changes in the staircase profile of the hair bundle along the apical portion of the chick's basilar papilla. Images of hair cells from 8 discretely dissected segments of the apical 3rd of the basilar papilla were archived, and the profile contour outlined by the tips of the stereocilia was digitised and curves were fitted by linear and power equations. The hair bundles of tall hair cells exhibited both linear and curvilinear profiles, which were equally distributed along the papilla. All short hair cells in our sample had straight contours. The differences in hair bundle shape among the tall hair cells may lead to differential susceptibility to injury and some variance in the current-displacement transduction curves due to differences in the translation of forces throughout the hair bundle. PMID:11215761

  4. Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. II. Impact of exercise training in obesity.

    PubMed

    Padilla, Jaume; Jenkins, Nathan T; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Davis, J Wade; Laughlin, M Harold

    2014-04-15

    We employed next-generation RNA sequencing (RNA-Seq) technology to determine the extent to which exercise training alters global gene expression in skeletal muscle feed arteries and aortic endothelial cells of obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Transcriptional profiles of the soleus and gastrocnemius muscle feed arteries (SFA and GFA, respectively) and aortic endothelial cell-enriched samples from rats that underwent an endurance exercise training program (EndEx; n = 12) or a interval sprint training program (IST; n = 12) or remained sedentary (Sed; n = 12) were examined. In response to EndEx, there were 39 upregulated (e.g., MANF) and 20 downregulated (e.g., ALOX15) genes in SFA and 1 upregulated (i.e., Wisp2) and 1 downregulated (i.e., Crem) gene in GFA [false discovery rate (FDR) < 10%]. In response to IST, there were 305 upregulated (e.g., MANF, HSPA12B) and 324 downregulated genes in SFA and 101 upregulated and 66 downregulated genes in GFA, with an overlap of 32 genes between arteries. Furthermore, in aortic endothelial cells, there were 183 upregulated (e.g., eNOS, SOD-3) and 141 downregulated (e.g., ATF3, Clec1b, npy, leptin) genes with EndEx and 71 upregulated and 69 downregulated genes with IST, with an overlap of 35 between exercise programs. Expression of only two genes (Tubb2b and Slc9a3r2) was altered (i.e., increased) by exercise in all three arteries. The finding that both EndEx and IST produced greater transcriptional changes in the SFA compared with the GFA is intriguing when considering the fact that treadmill bouts of exercise are associated with greater relative increases in blood flow to the gastrocnemius muscle compared with the soleus muscle.

  5. Aldosterone alters the participation of endothelial factors in noradrenaline vasoconstriction differently in resistance arteries from normotensive and hypertensive rats.

    PubMed

    Xavier, Fabiano E; Blanco-Rivero, Javier; Avendaño, María Soledad; Sastre, Esther; Yela, Rubén; Velázquez, Kyra; Salaíces, Mercedes; Balfagón, Gloria

    2011-03-11

    This study analyzed the effect of aldosterone (0.05mg/kg per day, 3 weeks) on vasoconstriction induced by noradrenaline in mesenteric resistance arteries from WKY rats and SHR. Contraction to noradrenaline was measured in mesenteric resistance arteries from untreated and aldosterone-treatedrats from both strains. Participation of nitric oxide (NO), superoxide anions, thromboxane A(2) (TxA(2)) and prostacyclin in this response was determined. 6-keto-prostaglandin (PG)F1alpha and thromboxane B(2) (TxB(2)) releases were determined by enzyme immunoassay. NO and superoxide anion release were also determined by fluorescence and chemiluminiscence, respectively. Aldosterone did not modify noradrenaline-induced contraction in either strain. In mesenteric resistance arteries from both aldosterone-treated groups, endothelium removal or preincubation with NO synthesis inhibitor L-NAME increased the noradrenaline-induced contraction, while incubation with the superoxide anion scavenger tempol decreased it. Preincubation with either the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively) decreased the noradrenaline contraction in aldosterone-treated animals, while this response was not modified by COX-1 inhibitor SC-560. TxA(2) synthesis inhibitor (furegrelate), or TxA2 receptor antagonist (SQ 29 548) also decreased the noradrenaline contraction in aldosterone-treated animals. In untreated SHR, but not WKY rats, this response was increased by L-NAME, and reduced by tempol, indomethacin, NS-398 or SQ 29 548. Aldosterone treatment did not modify NO or TxB(2) release, but it did increase superoxide anion and 6-keto-PGF(1alpha) release in mesenteric resistance arteries from both strains. In conclusion, chronic aldosterone treatment reduces smooth muscle contraction to alpha-adrenergic stimuli, producing a new balance in the release of endothelium-derived prostanoids and NO.

  6. Involvement of IP3-receptor activation in endothelin-1-induced Ca(2+) influx in rat pulmonary small artery.

    PubMed

    Kato, K; Okamura, K; Hatta, M; Morita, H; Kajioka, S; Naito, S; Yamazaki, J

    2013-11-15

    We examined the endothelin-1 (ET-1)-induced increase in the intracellular free Ca(2+) concentration ([Ca(2+)]i) in fura-2-loaded rat pulmonary small arteries. ET-1 (30 nM) elicited a long-lasting increase in [Ca(2+)]i in physiological salt solution (PSS). In subsequent experiments, arteries were pretreated with BQ-788, an ETB-specific blocker, to allow us to focus on responses mediated via the ETA receptor, the existence of which was confirmed by immunohistochemistry. In Ca(2+)-free PSS, ET-1 evoked a small transient increase in [Ca(2+)]i, indicating Ca(2+) release from the SR (sarcoplasmic reticulum). After a switch to PSS (containing 2mM CaCl2), ET-1 elicited a long-lasting increase in [Ca(2+)]i that was not inhibited by 1 μM nicardipine, an L-type Ca(2+)-channel inhibitor, suggesting involvement of a Ca(2+)-influx pathway independent of that channel. In arteries preincubated with 30 μM cyclopiazonic acid (CPA) or 2 μM thapsigargin (TG), the ET-1-induced Ca(2+)-release was greatly reduced, and the induced Ca(2+)-influx was attenuated. U-73122, a phospholipase C (PLC) inhibitor, had inhibitory effects similar to those of CPA and TG on the ET-1-induced Ca(2+)-release and Ca(2+)-influx, whereas U-73343, an inactive analogue of U-73122, had no such effects. Two putative membrane-permeable IP3-receptor blockers, 2-aminoethoxydiphenyl borate (2APB, 50 μM) and Xestospongin C (20 μM), (a) almost completely inhibited the ET-1-induced Ca(2+)-release and Ca(2+)-influx, and (b) reduced the ET-1-induced contraction. These results indicate that in rat pulmonary small arteries, ET-1 induces receptor-operated Ca(2+) influx via the ETA receptor, and that this influx interacts with InsP3-receptor activation. PMID:24157978

  7. Morphometric and ultrastructural analysis of the effect of bromocriptine and cyclosporine on the vasospastic femoral artery of rats

    PubMed Central

    Tokmak, Mehmet; Başocak, Kahan; Canaz, Hüseyin; Canaz, Gökhan; İplikçioğlu, Celal

    2015-01-01

    Vasospasm is the main causes of mortality and morbidity in patiens with subarachnoid hemorrhage (SAH). The arterial narrowing mechanism that develops after SAH is not yet fully understood but many studies showed that hypotension, neurogenic reflexes, clots in the subarachnoidal space, spasmogenic agents, humoral and celluler immunity play a role in the etiology. In this study we investigate the effects of Bromocriptine and Cyclosporine A in vasospasm secondary to SAH on rat femoral artery from ultrastructural and morphometric perspectives. 120 male Sprague-Dawley rats divided into 12 groups: Vasospasm (V), control (K), surgical control (CK) groups, vasospasm+Bromocriptine and/or Cyclosporine-A groups (VCyA, VBr, VBr+CyA), Bromocriptine and/or Cyclosporine-A control groups (CK, BK, Br+CyAK), Bromocriptine and/or Cyclosporine-A surgical control groups (BCK, CyCK, Br+CyACK). In order to create SAH model, 0, 1 cm3 blood injected into silastic sheath wrapped rat femoral artery. Bromocriptine (2 mg/kg/d) and Cyclosporine A (10 mg/kg/d) combinations applied to control, surgical control and vasospastic models. Light microscopy, transmission electron microscopy and scanning electron microscopy used during this study. Statistical evaluation of the morphometric measurement data concerning vascular wall thickness and luminal cross-sectional areas of all groups were performed using Mann-Whitney U, Wilcoxon-signed rank, and Student-t tests. Cyclosporine A, whose effects in the prevention of vasospasm have been demonstrated in previous studies. In this study we discovered that Bromocriptine demonstrated strong effects similar to Cyclosporine-A. Bromocriptine and Cyclosporine A markedly prevent the development of chronic morphologic vasospasm following SAH. The combined use of both drugs does not change this preventive effect. PMID:26770311

  8. Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species

    PubMed Central

    Furieri, Lorena B; Galán, María; Avendaño, María S; García-Redondo, Ana B; Aguado, Andrea; Martínez, Sonia; Cachofeiro, Victoria; Bartolomé, M Visitación; Alonso, María J; Vassallo, Dalton V; Salaices, Mercedes

    2011-01-01

    BACKGROUND AND PURPOSE Exposure to mercury is known to increase cardiovascular risk but the underlying mechanisms are not well explored. We analysed whether chronic exposure to low mercury doses affects endothelial modulation of the coronary circulation. EXPERIMENTAL APPROACH Left coronary arteries and hearts from Wistar rats treated with either HgCl2 (first dose 4.6 µg·kg−1, subsequent doses 0.07 µg·kg−1 day−1, 30 days) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl2 were also used. KEY RESULTS Mercury treatment increased 5-HT-induced vasoconstriction but reduced acetylcholine-induced vasodilatation. It also reduced nitric oxide (NO) production and the effects of NO synthase inhibition with L-NAME (100 µmol·L−1) on 5-HT and acetylcholine responses. Superoxide anion production and mRNA levels of NOX-1 and NOX-4 were all increased. The superoxide anion scavenger tiron (1 mmol·L−1) reduced 5-HT responses and increased acetylcholine responses only in vessels from mercury-treated rats. In isolated hearts from mercury-treated rats, coronary perfusion and diastolic pressure were unchanged, but developed isovolumetric systolic pressure was reduced. In these hearts, L-NAME increased coronary perfusion pressure and diastolic pressure while it further reduced developed systolic pressure. CONCLUSIONS AND IMPLICATIONS Chronic exposure to low doses of mercury promotes endothelial dysfunction of coronary arteries, as shown by decreased NO bioavailability induced by increased oxidative stress. These effects on coronary function increase resistance to flow, which under overload conditions might cause ventricular contraction and relaxation impairment. These findings provide further evidence that mercury, even at low doses, could be an environmental risk factor for cardiovascular disease. PMID:21232032

  9. Endovascular coiling of a ruptured basilar apex aneurysm with associated pseudoaneurysm.

    PubMed

    Yanamadala, Vijay; Lin, Ning; Zarzour, Hekmat; Frerichs, Kai U; Walcott, Brian P; Thomas, Ajith J; Puri, Ajit S

    2014-09-01

    Acute intracranial pseudoaneurysms secondary to aneurysmal rupture are a rare entity with no clear evidence-based guidelines for treatment to our knowledge. There are numerous examples of successful treatment of pseudoaneurysms both surgically and endovascularly, the latter mainly within the anterior circulation. Risk of pseudoaneurysm rupture in the acute state during endovascular procedures with subsequent difficulty in controlling the bleeding without sacrificing the feeder artery has led to some reservation in using endovascular treatments more broadly. We report a rare case of a 52-year-old-woman who presented with acute subarachnoid hemorrhage and was found to have a ruptured 5 mm × 8 mm bi-lobulated basilar apex aneurysm on CT angiography. Digital subtraction angiography demonstrated an associated anterior pseudoaneurysm that was formed secondary to the aneurysm rupture. The true aneurysm was successfully coiled with careful avoidance of the pseudoaneurysmal sac. Pseudoaneurysms are frequently identified for the first time during digital subtraction angiography. Recognizing their presence is essential for treatment planning. Acute pseudoaneurysms associated with true aneurysmal rupture can be safely and successfully treated by endovascular coiling of the true aneurysm. Care must be taken to avoid manipulation of the pseudoaneurysmal sac during the embolization.

  10. The effect of different amounts of calcium intake on bone metabolism and arterial calcification in ovariectomized rats.

    PubMed

    Agata, Umon; Park, Jong-Hoon; Hattori, Satoshi; Iimura, Yuki; Ezawa, Ikuko; Akimoto, Takayuki; Omi, Naomi

    2013-01-01

    Low calcium (Ca) intake is the one of risk factors for both bone loss and medial elastocalcinosis in an estrogen deficiency state. To examine the effect of different amounts of Ca intake on the relationship between bone mass alteration and medial elastocalcinosis, 6-wk-old female SD rats were randomized into ovariectomized (OVX) control or OVX treated with vitamin D(3) plus nicotine injection (VDN) groups. The OVX treated with VDN group was then divided into 5 groups depending on the different Ca content in their diet, 0.01%, 0.1%, 0.6%, 1.2%, and 2.4% Ca intakes. After 8 wk of experimentation, the low Ca intake groups of 0.01% and 0.1% showed a low bone mineral density (BMD) and bone properties significantly different from those of the other groups, whereas the high Ca intake groups of 1.2% and 2.4% showed no difference compared with the OVX control. Only in the 0.01% Ca intake group, a significantly higher Ca content in the thoracic artery was found compared with that of the OVX control. Arterial tissues of the 0.01% Ca intake group showed an increase of bone-specific alkaline phosphatase (BAP) activity, a marker of bone mineralization, associated with arterial Ca content. However, the high Ca intake did not affect arterial Ca content nor arterial BAP activity. These results suggested that a low Ca intake during periods of rapid bone loss caused by estrogen deficiency might be one possible cause for the complication of both bone loss and medial elastocalcinosis.

  11. Vasorelaxation to N-oleoylethanolamine in rat isolated arteries: mechanisms of action and modulation via cyclooxygenase activity

    PubMed Central

    Wheal, AJ; Alexander, SPH; Randall, MD

    2010-01-01

    Background and purpose: The endocannabinoid-like molecule N-oleoylethanolamine (OEA) is found in the small intestine and regulates food intake and promotes weight loss. The principal aim of the present study was to evaluate the vascular effects of OEA. Experimental approach: Perfused isolated mesenteric arterial beds were pre-contracted with methoxamine or high potassium buffers and concentration-response curves to OEA were constructed. Combinations of inhibitors to block nitric oxide production, sensory nerve activity, cyclooxygenase activity, potassium channels, chloride channels and gap junctions, and a cannabinoid CB1 receptor antagonist, were used during these experiments. The effects of OEA on caffeine-induced contractions in calcium-free buffer were also assessed. Isolated thoracic aortic rings were used as a comparison. Key results: OEA caused concentration-dependent vasorelaxation in rat isolated mesenteric arterial beds and thoracic aortic rings, with a greater maximal response in mesenteric vessels. This relaxation was sensitive to inhibition of sensory nerve activity and endothelial removal in both preparations. The cyclooxygenase inhibitor indomethacin reversed the effects of capsaicin pre-treatment in perfused mesenteric arterial beds and indomethacin alone enhanced vasorelaxation to OEA. The OEA-induced vasorelaxation was inhibited by a CB1 receptor antagonist only in aortic rings. In mesenteric arteries, OEA suppressed caffeine-induced contractions in calcium-free buffer. Conclusions and implications: The vasorelaxant effects of OEA are partly dependent on sensory nerve activity and a functional endothelium in the vasculature. In addition, vasorelaxation to OEA is enhanced following cyclooxygenase inhibition. OEA may also interfere with the release of intracellular calcium in arterial preparations. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476

  12. Identification of L- and T-type Ca2+ channels in rat cerebral arteries: role in myogenic tone development.

    PubMed

    Abd El-Rahman, Rasha R; Harraz, Osama F; Brett, Suzanne E; Anfinogenova, Yana; Mufti, Rania E; Goldman, Daniel; Welsh, Donald G

    2013-01-01

    L-type Ca(2+) channels are broadly expressed in arterial smooth muscle cells, and their voltage-dependent properties are important in tone development. Recent studies have noted that these Ca(2+) channels are not singularly expressed in vascular tissue and that other subtypes are likely present. In this study, we ascertained which voltage-gated Ca(2+) channels are expressed in rat cerebral arterial smooth muscle and determined their contribution to the myogenic response. mRNA analysis revealed that the α(1)-subunit of L-type (Ca(v)1.2) and T-type (Ca(v)3.1 and Ca(v)3.2) Ca(2+) channels are present in isolated smooth muscle cells. Western blot analysis subsequently confirmed protein expression in whole arteries. With the use of patch clamp electrophysiology, nifedipine-sensitive and -insensitive Ba(2+) currents were isolated and each were shown to retain electrical characteristics consistent with L- and T-type Ca(2+) channels. The nifedipine-insensitive Ba(2+) current was blocked by mibefradil, kurtoxin, and efonidpine, T-type Ca(2+) channel inhibitors. Pressure myography revealed that L-type Ca(2+) channel inhibition reduced tone at 20 and 80 mmHg, with the greatest effect at high pressure when the vessel is depolarized. In comparison, the effect of T-type Ca(2+) channel blockade on myogenic tone was more limited, with their greatest effect at low pressure where vessels are hyperpolarized. Blood flow modeling revealed that the vasomotor responses induced by T-type Ca(2+) blockade could alter arterial flow by ∼20-50%. Overall, our findings indicate that L- and T-type Ca(2+) channels are expressed in cerebral arterial smooth muscle and can be electrically isolated from one another. Both conductances contribute to myogenic tone, although their overall contribution is unequal. PMID:23103495

  13. High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery.

    PubMed

    Yasuda, Yoshitaka; Feng, Guo-Gang; Li, Jiazheng; Nakamura, Emi; Hayashi, Hisaki; Sato, Motohiko; Fujiwara, Yoshihiro; Kinoshita, Hiroyuki

    2016-09-01

    Whether high oxygen is harmful to the vascular function is unclear. The present study examined if high oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production. Rat mesenteric arteries with endothelium at 95 or 50 % oxygen were subjected to isometric force recordings, measurement of thromboxane B2 levels, determination of superoxide and peroxynitrite levels and evaluation of NADPH oxidase subunit protein expression, respectively. L-cysteine (0.01-3 mM) constricted or dilated arteries at 95 and 50 % oxygen, respectively. Thromboxane receptor antagonist SQ-29,548 (1 μM) abolished the constriction at 95 % oxygen. L-cysteine (3 mM) increased levels of thromboxane B2 in arteries upon 95 % oxygen application. L-cysteine relaxed arteries treated with superoxide inhibitor tiron (2 mM) or NADPH oxidase inhibitor gp91ds-tat (1 μM) irrespective of the oxygen concentration while ATP-sensitive K(+) channel inhibitor glibenclamide (1 μM) and cystathionine-γ-lyase (CSE) inhibitor DL-propargylglycine (10 mM) similarly abolished the relaxation. L-cysteine (3 mM) with 95 % oxygen augmented levels of superoxide as well as nitrotyrosine within the artery, concomitantly with enhanced membrane protein expression of NADPH oxidase subunit p47phox. The higher concentration of oxygen attenuates L-cysteine-induced vasodilation via superoxide production mediated by NADPH oxidase along with thromboxane A2 production, resulting in vasoconstriction. The increased levels of superoxide, as well as peroxynitrite, coexist with the impaired vasodilation related to ATP-sensitive K(+) channels and CSE. Higher oxygen with plasma cysteine may cause oxidative stress and vasoconstrictor prostanoid production in blood vessels.

  14. High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery.

    PubMed

    Yasuda, Yoshitaka; Feng, Guo-Gang; Li, Jiazheng; Nakamura, Emi; Hayashi, Hisaki; Sato, Motohiko; Fujiwara, Yoshihiro; Kinoshita, Hiroyuki

    2016-09-01

    Whether high oxygen is harmful to the vascular function is unclear. The present study examined if high oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production. Rat mesenteric arteries with endothelium at 95 or 50 % oxygen were subjected to isometric force recordings, measurement of thromboxane B2 levels, determination of superoxide and peroxynitrite levels and evaluation of NADPH oxidase subunit protein expression, respectively. L-cysteine (0.01-3 mM) constricted or dilated arteries at 95 and 50 % oxygen, respectively. Thromboxane receptor antagonist SQ-29,548 (1 μM) abolished the constriction at 95 % oxygen. L-cysteine (3 mM) increased levels of thromboxane B2 in arteries upon 95 % oxygen application. L-cysteine relaxed arteries treated with superoxide inhibitor tiron (2 mM) or NADPH oxidase inhibitor gp91ds-tat (1 μM) irrespective of the oxygen concentration while ATP-sensitive K(+) channel inhibitor glibenclamide (1 μM) and cystathionine-γ-lyase (CSE) inhibitor DL-propargylglycine (10 mM) similarly abolished the relaxation. L-cysteine (3 mM) with 95 % oxygen augmented levels of superoxide as well as nitrotyrosine within the artery, concomitantly with enhanced membrane protein expression of NADPH oxidase subunit p47phox. The higher concentration of oxygen attenuates L-cysteine-induced vasodilation via superoxide production mediated by NADPH oxidase along with thromboxane A2 production, resulting in vasoconstriction. The increased levels of superoxide, as well as peroxynitrite, coexist with the impaired vasodilation related to ATP-sensitive K(+) channels and CSE. Higher oxygen with plasma cysteine may cause oxidative stress and vasoconstrictor prostanoid production in blood vessels. PMID:27389323

  15. Surfactant reduction of cerebral infarct size and behavioral deficit in a rat model of cerebrovascular arterial gas embolism

    PubMed Central

    Armstead, Stephen C.

    2013-01-01

    Gas embolism occurs commonly in cardiac and vascular surgery and decompression sickness. The goals of this study were to develop a new in vivo rat model of cerebrovascular arterial gas embolism and to determine the effects of exogenous surfactants on resultant brain infarct volume and accompanying long-term neurological dysfunction using the model. Unilateral cerebral arterial gas embolism was induced in Sprague Dawley rats, including groups receiving intravenous Pluronic F-127 (PF-127) and Oxycyte perflourocarbon surfactant pretreatment. Magnetic resonance imaging (MRI) was performed at 24 and 72 h postembolism to determine infarct volume. The elevated body swing test (EBST), limb-placement test, proprioception forelimb and hindlimb tests, whisker tactile test, and Morris Water Maze test were performed to assess motor behavior, somatosensory deficit, and spatial cognitive function out to 29 days after embolization. A stable stroke model was developed with MRI examination revealing infarction in the ipsilateral cerebral hemisphere. Gas embolized rats had significant cognitive and sensorimotor dysfunction, including approximately threefold increase in Morris Water Maze latency time, ∼20% left-sided biasing in EBST performance, 0.5 to 1.5 (mean) point score elevations in the proprioception and whisker tactile tests, and 3.0 point (mean) elevation in the limb-placement test, all of which were persistent throughout the postembolic period. Surfactant prophylaxis with either PF-127 or Oxycyte rendered stroke undetectable by MRI scanning and markedly reduced the postembolic deficits in both cognitive and sensorimotor performance in treated rats, with normalization of EBST and whisker tactile tests within 7 days. PMID:23845977

  16. Persistent Primitive Hypoglossal Artery (PPHA) - A Rare Anomaly with Literature Review.

    PubMed

    Srinivas, M R; Vedaraju, K S; Manjappa, B H; Nagaraj, B R

    2016-01-01

    Persistent primitive hypoglossal artery (PPHA) is a rare embryonic carotid vertebrobasilar artery anastomosis. Hypoglossal artery arises from the internal carotid artery (ICA) between the C1 and C2 vertebral levels and traverses through the hypoglossal canal to join the vertebro-basilar system. We present a rare case of an anomalous right sided PPHA as a sole supply to posterior circulation of brain with absent/hypoplastic bilateral vertebral arteries in a two year child who had presented with acute left sided haemiplegia. Three dimensional time of flight magnetic resonance angiography identified an anomalous vessel arising from the right internal carotid artery at the level of axis vertebra and joining the vertebra-basilar arterial system after coursing through the right hypoglossal canal. This anomaly when present may predispose the person to aneurysm formation, ischaemia in the posterior circulation and atherosclerotic disease of the intracranial vessels. PMID:26894148

  17. Persistent Primitive Hypoglossal Artery (PPHA) – A Rare Anomaly with Literature Review

    PubMed Central

    Vedaraju, KS; Manjappa, BH; Nagaraj, BR

    2016-01-01

    Persistent primitive hypoglossal artery (PPHA) is a rare embryonic carotid vertebrobasilar artery anastomosis. Hypoglossal artery arises from the internal carotid artery (ICA) between the C1 and C2 vertebral levels and traverses through the hypoglossal canal to join the vertebro-basilar system. We present a rare case of an anomalous right sided PPHA as a sole supply to posterior circulation of brain with absent/hypoplastic bilateral vertebral arteries in a two year child who had presented with acute left sided haemiplegia. Three dimensional time of flight magnetic resonance angiography identified an anomalous vessel arising from the right internal carotid artery at the level of axis vertebra and joining the vertebra-basilar arterial system after coursing through the right hypoglossal canal. This anomaly when present may predispose the person to aneurysm formation, ischaemia in the posterior circulation and atherosclerotic disease of the intracranial vessels. PMID:26894148

  18. Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats.

    PubMed

    Lee, Choong-Ku; Park, Kwang-Hwa; Baik, Soon-Koo; Jeong, Seong-Woo

    2016-06-01

    Cardiovascular autonomic dysfunction, which is manifested by an impairment of the arterial baroreflex, is prevalent irrespective of etiology and contributes to the increased morbidity and mortality in cirrhotic patients. However, the cellular mechanisms that underlie the cirrhosis-impaired arterial baroreflex remain unknown. In the present study, we examined whether the cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. Biliary and nonbiliary cirrhotic rats were generated via common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Histological and molecular biological examinations confirmed the development of fibrosis in the livers of both cirrhotic rat models. The heart rate changes during phenylephrine-induced baroreceptor activation indicated that baroreflex sensitivity was blunted in the CBDL and TAA rats. Under the current-clamp mode of the patch-clamp technique, cell excitability was recorded in DiI-labeled AB neurons. The number of action potential discharges in the A- and C-type AB neurons was significantly decreased because of the increased rheobase and threshold potential in the CBDL and TAA rats compared with sham-operated rats. Real-time PCR and Western blotting indicated that the NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly downregulated in the nodose ganglion neurons from the CBDL and TAA rats compared with the sham-operated rats. Consistent with these molecular data, the tetrodotoxin-sensitive NaV currents and the tetrodotoxin-resistant NaV currents were significantly decreased in A- and C-type AB neurons, respectively, from the CBDL and TAA rats compared with the sham-operated rats. Taken together, these findings implicate a key cellular mechanism in the cirrhosis-impaired arterial baroreflex. PMID:26984890

  19. Upregulation of ERK1/2-eNOS via AT2 Receptors Decreases the Contractile Response to Angiotensin II in Resistance Mesenteric Arteries from Obese Rats

    PubMed Central

    Hagihara, Graziela N.; Lobato, Nubia S.; Filgueira, Fernando P.; Akamine, Eliana H.; Aragão, Danielle S.; Casarini, Dulce E.; Carvalho, Maria Helena C.; Fortes, Zuleica B.

    2014-01-01

    It has been clearly established that mitogen-activated protein kinases (MAPKS) are important mediators of angiotensin II (Ang II) signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese) and non-obese Wistar rats (control) were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats. PMID:25170617

  20. Vertebro-Basilar Junction Aneurysms: A Single Centre Experience and Meta-Analysis of Endovascular Treatments

    PubMed Central

    Graziano, Francesca; Ganau, Mario; Iacopino, Domenico Gerardo; Boccardi, Edoardo

    2014-01-01

    Summary Vascular lesions of the vertebrobasilar junction (VBJ) are challenging in neurosurgical practice, and their gold-standard therapy is still under debate. We describe the operative strategies currently in use for the management of these complex vascular lesions and discuss their rationale in a literature meta-analysis and single centre blinded retrospective study. The single centre study included a review of initial presentation, angiographic features and clinical outcome (with modified Rankin Scale [mRS] scores) over a long-term follow-up. In our series, small aneurysms were effectively treated by endosaccular coil embolization, whereas a strategy including flow-diverter devices combined with endosaccular coil embolization was the option of choice in large and giant aneurysms, leading to satisfactory outcomes in most cases. Our Medline review showed that endovascular treatment was chosen in most VBJ cases, whereas the microsurgical option was assigned to only a few cases. Among the endovascular treatments, the most common techniques used for the treatment of VBJ aneurysms were: coiling, stent-assisted coiling and flow diversion. Our study highlights that aneurysm morphology, location and patient-specific angio-architecture are key factors to be considered in the management of VBJ aneurysms. Most case series, including our own, show that parent artery reconstruction using a flow-diverter device is a feasible and successful technique in some cases of giant and complex aneurysms (especially those involving the lower third of the basilar artery) while a "sit back, wait and see" approach may represent the safest and most reasonable option. PMID:25489898

  1. Mixing during intravertebral arterial infusions in an in vitro model.

    PubMed

    Lutz, Robert J; Warren, Kathy; Balis, Frank; Patronas, Nicholas; Dedrick, Robert L

    2002-06-01

    Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments. PMID:12164691

  2. Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats.

    PubMed

    Yasuda, Nodoka; Ishii, Takayuki; Oyama, Dai; Fukuta, Tatsuya; Agato, Yurika; Sato, Akihiko; Shimizu, Kosuke; Asai, Tomohiro; Asakawa, Tomohiro; Kan, Toshiyuki; Yamada, Shizuo; Ohizumi, Yasushi; Oku, Naoto

    2014-04-22

    Nobiletin, a citrus polymethoxylated flavone, is reported to possess various pharmacological activities such as anticancer, anti-inflammation, and antioxidant effects. Recently, nobiletin was shown to provide therapeutic benefit for the treatment of Alzheimer׳s disease by activating cAMP-response element-binding protein (CREB). In the present study, we investigated whether nobiletin could protect the brain against ischemia-reperfusion (I/R) injury and improve functional outcome in cerebral I/R model rats, since CREB activation is known to protect neuronal cells in cerebral ischemia. Nobiletin was injected twice at 0 and 1h after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. Cerebral I/R induced prominent brain damage in the ischemic hemisphere of t-MCAO rat brains; however, nobiletin treatment significantly reduced the infarct volume and suppressed the brain edema. Immunohistochemical and TUNEL staining indicated that nobiletin treatment significantly suppressed neutrophil invasion into the ischemic region and significantly decreased apoptotic brain cell death in ischemic hemisphere, suggesting that the anti-inflammatory effect and anti-apoptotic effect should be regarded as the neuroprotective mechanism of nobiletin. Moreover, nobiletin treatment ameliorated motor functional deficits in the ischemic rats compared with those deficits of the vehicle-treated group. These results indicate that nobiletin is a potential neuroprotectant for the treatment of cerebral I/R injury.

  3. Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion

    PubMed Central

    Ren, Changhong; Wang, Brian; Li, Ning; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Current studies demonstrated that traditional Chinese herbal formula Danggui-Shaoyao-San (DSS) is not only used for the treatment of menstrual disorder, but has also found its use in neurological diseases. However, the neuroprotective role of DSS on ischemia-induced brain injury is still unclear. The aim of the present study is to explore the effect of DSS in ischemic brain injury. Total 30 adult female Sprague–Dawley rats underwent 90 min transient middle cerebral artery occlusion (MCAO). DSS (600 mg/kg) was administered through the intragastric route at the time of reperfusion and then performed every day thereafter until sacrifice. Results showed that DSS treatment significantly improved neurobehavioral outcomes (N=10 per group, P<0.05). Immunohistochemical staining showed that microvessel density in the perifocal region of DSS-treated rats was significantly increased compared to the saline-treated group (N=4 per group, P<0.01). Similarly, the numbers of BrdU+/DCX+ cells in the subventricular zone were increased in DSS-treated rats compared to the saline-treated group (P<0.05). Furthermore, we demonstrated that DSS treatment activated vascular endothelial growth factor (N=4 per group, P<0.05) and promoted eNOS phosphorylation (N=4 per group, P<0.05). Thus, we concluded that DSS promoted focal angiogenesis and neurogenesis, and attenuated ischemia-induced brain injury in rats after MCAO, suggesting that DSS is a potential drug for ischemic stroke therapy. PMID:26236546

  4. Interactions between neuropeptide Y and the adenylate cyclase pathway in rat mesenteric small arteries: role of membrane potential.

    PubMed Central

    Prieto, D; Buus, C; Mulvany, M J; Nilsson, H

    1997-01-01

    1. Simultaneous measurements of membrane potential and tension were performed to investigate the intracellular mechanisms of neuropeptide Y (NPY) in rat mesenteric small arteries. 2. NPY (0.1 microM) depolarized arterial smooth muscle cells from -55 to -47 mV and increased wall tension by 0.22 N m-1, representing 11% of the contraction elicited by a high-potassium solution. Isoprenaline (1 microM) and acetylcholine (1 microM) evoked hyperpolarizations of 11 and 17 mV, respectively. NPY inhibited the isoprenaline-induced effects on membrane potential without affecting those of acetylcholine. 3. Forskolin evoked sustained concentration-dependent hyperpolarizations of small mesenteric arteries. NPY (0.1 microM) inhibited the responses to 1 microM forskolin, but did not alter the stable hyperpolarization elicited by the specific activator of protein kinase A (PKA) SP-5,6-DCl-cBIMPS (0.1 mM). Forskolin increased the cyclic AMP (cAMP) content of the arteries 21-fold, and NPY inhibited the forskolin-evoked increase in cAMP levels by 91%. 4. The hyperpolarization produced by 1 microM forskolin was not affected by either charybdotoxin (0.1 microM) or 4-aminopyridine (0.5 mM), but glibenclamide (5 microM) inhibited the hyperpolarization by 70%. Glibenclamide also inhibited the hyperpolarization evoked by SP-5,6-DCl-cBIMPS by 59%. 5. Neither depolarization nor contraction caused by NPY were significantly affected by either glibenclamide (5 microM) or nifedipine (1 microM), but they were reduced by gadolinium (10 microM). However, the blocking effect of NPY on forskolin-elicited hyperpolarization was not affected by gadolinium. 6. Charybdotoxin (0.1 microM) and 4-aminopyridine (0.5 mM) strongly enhanced the depolarization and contraction caused by NPY (0.1 microM), and nifedipine (1 microM) prevented the enhanced responses to NPY in the presence of charybdotoxin. 7. These findings suggest that NPY acts through at least two different intracellular mechanisms in mesenteric small

  5. Iron-induced remodeling in cultured rat pulmonary artery endothelial cells.

    PubMed

    Gorbunov, Nikolai V; Atkins, James L; Gurusamy, Narasimman; Pitt, Bruce R

    2012-02-01

    Although iron is known to be a component of the pathogenesis and/or maintenance of acute lung injury (ALI) in experimental animals and human subjects, the majority of these studies have focused on disturbances in iron homeostasis in the airways resulting from exposure to noxious gases and particles. Considerably less is known about the effect of increased plasma levels of redox-reactive non-transferrin bound iron (NTBI) and its impact on pulmonary endothelium. Plasma levels of NTBI can increase under various pathophysiological conditions, including those associated with ALI, and multiple mechanisms are in place to affect the [Fe(2+)]/[Fe(3+)] redox steady state. It is well accepted, however, that intracellular transport of NTBI occurs after reduction of [Fe(3+)] to [Fe(2+)] (and is mediated by divalent metal transporters). Accordingly, as an experimental model to investigate mechanisms mediating vascular effects of redox reactive iron, rat pulmonary artery endothelial cells (RPAECs) were subjected to pulse treatment (10 min) with [Fe(2+)] nitriloacetate (30 μM) in the presence of pyrithione, an iron ionophore, to acutely increase intracellular labile pool of iron. Cellular iron influx and cell shape profile were monitored with time-lapse imaging techniques. Exposure of RPAECs to [Fe(2+)] resulted in: (i) an increase in intracellular iron as detected by the iron sensitive fluorophore, PhenGreen; (ii) depletion of cell glutathione; and (iii) nuclear translocation of stress-response transcriptional factors Nrf2 and NFkB (p65). The resulting iron-induced cell alterations were characterized by cell polarization and formation of membrane cuplike and microvilli-like projections abundant with ICAM-1, caveolin-1, and F-actin. The iron-induced re-arrangements in cytoskeleton, alterations in focal cell-cell interactions, and cell buckling were accompanied by decrease in electrical resistance of RPAEC monolayer. These effects were partially eliminated in the presence of N

  6. Role of wall tension in the vasoconstrictor response of cannulated rat mesenteric small arteries.

    PubMed Central

    VanBavel, E; Mulvany, M J

    1994-01-01

    1. We have studied the influence of mechanical loading conditions on the responses of cannulated rat mesenteric small arteries to noradrenaline, vasopressin and potassium. 2. The cross-sectional area (CSA) of vessels was continuously monitored. Isometric loading (CSA-controlled conditions) or isobaric loading (pressure-controlled conditions) was achieved by feedback adjustment of the distending pressure. 3. Noradrenaline (0.3 microM) and vasopressin (0.05 u l-1) induced myogenic responsiveness, resulting in a constant or declining CSA with increasing pressure. Potassium (32 mM) induced weak myogenic responsiveness. 4. At a constant pressure of 60 cmH2O, noradrenaline and vasopressin concentration-response curves were graded, the concentration-response curves of individual vessels being extended over two to three decades. Sensitivity to the vasoconstrictors, expressed as pD2 values (-log10 EC50), averaged 6.45 +/- 0.18 log M and 1.27 +/- 0.20 log u l-1 for the noradrenaline and vasopressin concentration-response curves respectively. The isobaric pD2 for K+ was 1.54 +/- 0.07 log M. 5. During CSA-controlled conditions, noradrenaline and vasopressin induced all-or-none responses to stretch. Potassium induced graded responses to stretch. 6. During CSA-controlled conditions, noradrenaline and vasopressin concentration-response curves also showed all-or-none behaviour. Almost the full response occurred through only a doubling of the concentration. pD2 values were 6.88 +/- 0.38 log M (noradrenaline) and 1.87 +/- 0.43 log u l-1 (vasopressin). Isometric vessels were significantly more sensitive to noradrenaline and vasopressin than isobaric vessels. Isometric K+ curves were gradual. pD2 was 1.54 +/- 0.07 log M, a value not different from the isobaric value. 7. These findings can be explained by assuming that agonist sensitivity is wall tension dependent, such that sensitivity increases with increasing wall tension. This concept accounts for partial regulation of wall tension

  7. Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model

    PubMed Central

    Allen, Robert A.; Wu, Wei; Yao, Mingyi; Dutta, Debaditya; Duan, Xinjie; Bachman, Timothy N.; Champion, Hunter C.; Stolz, Donna B.; Robertson, Anne M.; Kim, Kang; Isenberg, Jeffrey S.; Wang, Yadong

    2013-01-01

    The objective of this study was to evaluate the long term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into “neoarteries” (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues. PMID:24119457

  8. Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism.

    PubMed

    Wang, Youhua; Wang, Shengpeng; Wier, W Gil; Zhang, Quanjiang; Jiang, Hongke; Li, Qiuxia; Chen, Shengfeng; Tian, Zhenjun; Li, Youyou; Yu, Xiaojiang; Zhao, Ming; Liu, Jinjun; Yang, Jing; Zhang, Jing; Zang, Weijin

    2010-12-01

    Myocardial infarction (MI) has been shown to induce endothelial dysfunction in peripheral resistance arteries and thus increase peripheral resistance. This study was designed to investigate the underlying mechanisms of post-MI-related dysfunctional dilatation of peripheral resistance arteries and, furthermore, to examine whether exercise may restore dysfunctional dilatation of peripheral resistance arteries. Adult male Sprague-Dawley rats were divided into three groups: sham-operated, MI, and MI + exercise. Ultrastructure and relaxation function of the mesenteric arteries, as well as phosphatidylinositol-3 kinase (PI3K), Akt kinases (Akt), endothelial nitric oxide synthase (eNOS) activity, and phosphorylation of PI3K, Akt, and eNOS by ACh were determined. Post-MI rats exhibited pronounced ultrastructural changes in mesenteric artery endothelial cells and endothelial dysfunction. In addition, the activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh were significantly attenuated in mesenteric arteries (P < 0.05-0.01). After 8 wk of exercise, not only did endothelial cells appeared more normal in structure, but also ameliorated post-MI-associated mesenteric arterial dysfunction, which were accompanied by elevated activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh (P < 0.05-0.01). Importantly, inhibition of either PI3K or eNOS attenuated exercise-induced restoration of the dilatation function and blocked PI3K, Akt, and eNOS phosphorylation by ACh in the mesenteric arteries. These data demonstrate that MI induces dysfunctional dilation of peripheral resistance arteries by degradation of endothelial structural integrity and attenuating PI3K-Akt-eNOS signaling. Exercise may restore dilatation function of peripheral resistance arteries by protecting endothelial structural integrity and increasing PI3K-Akt-eNOS signaling cascades.

  9. Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.

    PubMed

    Sung, Dong Jun; Noh, Hyun Ju; Kim, Jae Gon; Park, Sang Woong; Kim, Bokyung; Cho, Hana; Bae, Young Min

    2013-01-01

    Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP-sensitive K(+) channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, α-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway. PMID:24336234

  10. Effect of angiotensin II receptor blockade on the interaction between enalaprilat and doxazosin in rat tail arteries.

    PubMed

    Marwood, J F

    1998-01-01

    1. Previous work has shown that enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), potentiated the actions of alpha 1-adrenoceptor antagonists; it was hypothesized that angiotensin II (AngII) modulated the activity of alpha 1-adrenoceptors. This hypothesis was tested in Sprague-Dawley rat isolated perfused tail arteries using the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319. 2. Losartan had no alpha 1-adrenoceptor antagonist effects at concentrations below 1 mumol/L. Similarly, losartan (0.1 mumol/L) had no effect on the alpha 1-adrenoceptor antagonist action of doxazosin (1, 10 nmol/L) nor on the potentiation of doxazosin by enalaprilat (1 mumol/L). 3. PD123319 (0.1 mumol/L) had no alpha 1-adrenoceptor antagonist effect but altered the mode of action of the alpha 1-adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non-competitive antagonist, as evidenced by the reduced slope of the dose-response curve for the alpha 1-adrenoceptor agonist phenylephrine. 4. These results suggest that AngII can modulate alpha 1-adrenoceptor function in rat tail arteries via an indirect action at AT2 receptors. However, the present results do not rule out the involvement of bradykinin, endothelin or prostaglandin in the modulation of alpha 1-adrenoceptor function by angiotensin II.

  11. Inhibitory effect of Bailing capsule on hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells

    PubMed Central

    Li, Xiaohui; Peng, Kejun; Zhou, Yutian; Deng, Fengmei; Ma, Jiao

    2016-01-01

    Objectives: To investigated the effects of Bailing capsule on hypoxia-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs). Methods: This prospective study was performed at the Central Laboratory, Chengdu Medical College, Chengdu, China between April 2012 and November 2014. Ten healthy adult male Wistar rats were administrated with gastric perfusion of Bailing capsule to obtain serum containing the tested drugs. Proliferation of pulmonary arterial smooth muscle cells proliferation was measured using cell counting kit-8 assay. Production of reactive oxygen species (ROS) in rat PASMCs was determined through a fluorometric assay, whereas production of endothelin-1 (ET-1) was detected by ELISA and quantitative real-time PCR (qRT-PCR). Expression of proliferating cell nuclear antigen (PCNA), c-fos, and c-jun in PASMCs was also determined using immunohistochemistry staining and qRT-PCR. Results: We observed that the medicated serum obviously inhibited hypoxia-induced cell proliferation in a concentration-dependent manner. Moreover, the medicated serum significantly reduced hypoxia-induced production of ROS and ET-1, as well as expression of PCNA, c-fos, and c-jun, in PASMCs. Conclusion: Results demonstrated that Bailing capsule can inhibit hypoxia-induced PASMC proliferation possibly by suppressing ET-1 and ROS production and by inhibiting expression of PCNA, c-fos, and c-jun. These results suggest that Bailing possess antiproliferative property, which is probably one of the underlying mechanisms of Bailing capsule for the clinical treatment of chronic obstructive pulmonary disease. PMID:27146611

  12. Pharmacologic analysis of 7-O-ethyl-fangchinoline-induced vasodilation properties in isolated perfused common carotid arteries of Wistar Kyoto rats and spontaneously hypertensive rats.

    PubMed

    Matsuura, M; Zenda, H; Chiba, S

    1991-10-01

    Using the cannula insertion method, we investigated vascular effects of 7-O-ethyl-fangchinoline (TJN-220) derived from tetrandrine in isolated and perfused common carotid arteries of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). A single dose of TJN-220 caused a vasodilation in a dose-related manner in arteries preconstricted by phenylephrine. The vasodilation was not inhibited by propranolol, a potent beta-adrenoceptor antagonist. A potent alpha-antagonist bunazosin inhibited the vasoconstriction to norepinephrine while TJN-220 did not modify the norepinephrine-induced constriction, indicating TJN-220 had no alpha-blocking activity. A potent calcium entry blocker, diltiazem, markedly attenuated the KCl-induced vasoconstriction, and TJN-220 slightly but significantly attenuated the KCl-induced one in large doses. The vasodilation of TJN-220 was not abolished after removing the endothelium by an intraluminal administration of saponin, although the ACh-induced dilation was completely abolished by it. A comparison of vascular responses in WKY and SHR revealed no significant differences. From these results, it is concluded that 1) a new tetrandrine derivative, TJN-220 has relatively long-lasting vasorelaxant properties, 2) the dilatory effects might not be related to adrenergic, muscarinic or endothelium-dependent mechanisms, and 3) the effects might partially be due to calcium entry antagonistic properties. PMID:1806292

  13. Molecular and pharmacological evidence for MT1 melatonin receptor subtype in the tail artery of juvenile Wistar rats.

    PubMed

    Ting, K N; Blaylock, N A; Sugden, D; Delagrange, P; Scalbert, E; Wilson, V G

    1999-06-01

    1. In this study reverse transcriptase-polymerase chain reaction (RT-PCR) has been used to identify mt1 and MT2 receptor mRNA expression in the rat tail artery. The contributions of both receptors to the functional response to melatonin were examined with the putative selective MT2 receptor antagonists, 4-phenyl-2-propionamidotetraline (4-P-PDOT) and 2-benzyl-N-pentanoyltryptamine. In addition, the action of melatonin on the second messenger cyclic AMP was investigated. 2. Using RT-PCR, mt1 receptor mRNA was detected in the tail artery from seven rats. In contrast MT2 receptor mRNA was not detected even after nested PCR. 3. At low concentrations of the MT2 selective ligands, neither 10 nM 4-P-PDOT (pEC50=8.70+/-0.31 (control) vs 8.73+/-0.16, n=6) nor 60 nM 2-benzyl-NV-pentanoyltryptamine (pEC50= 8.53+/-0.20 (control) vs 8.83+/-0.38, n = 6) significantly altered the potency of melatonin in the rat tail artery. 4. At concentrations non-selective for mt1 and MT2 receptors. 4-P-PDOT (3 microM) and 2-benzyl-N-pentanoyltryptamine (5 microM) caused a significant rightward displacement of the vasoconstrictor effect of melatonin. In the case of 4-P-PDOT, the estimated pKB (6.17+/-0.16, n=8) is similar to the binding affinity for mt1 receptor. 5. Pre-incubation with 1 microM melatonin did not affect the conversion of [3H]-adenine to [3H]-cyclic AMP under basal condition (0.95+/-0.19% conversion (control) vs 0.92+/-0.19%, n=4) or following exposure to 30 microM forskolin (5.20+/-1.30% conversion (control) vs 5.35+/-0.90%, n=4). 6. Based on the above findings, we conclude that melatonin receptor on the tail artery belongs to the MT1 receptor subtype, and that this receptor is probably independent of the adenylyl cyclase pathway.

  14. Arterial relationships to the nerves and some rigid structures in the posterior cranial fossa.

    PubMed

    Surchev, N

    2008-09-01

    The close relationships between the cranial nerves and the arterial vessels in the posterior cranial fossa are one of the predisposing factors for artery-nerve compression. The aim of this study was to examine the relationships of the vertebral and basilar arteries to some skull and dural structures and the nerves in the posterior cranial fossa. For this purpose, the skull bases and brains of 70 cadavers were studied. The topographic relationships of the vertebral and basilar arteries to the cranial nerves in the posterior cranial fossa were studied and the distances between the arteries and some osseous formations were measured. The most significant variations in arterial position were registered in the lower half of the basilar artery. Direct contact with an artery was established for the hypoglossal canal, jugular tubercle, and jugular foramen. The results reveal additional information about the relationships of the nerves and arteries to the skull and dural formations in the posterior cranial fossa. New quantitative information is given to illustrate them. The conditions for possible artery-nerve compression due to arterial dislocation are discussed and two groups (lines) of compression points are suggested. The medial line comprises of the brain stem points, usually the nerve root entry/exit zone. The lateral line includes the skull eminences, on which the nerves lie, or skull and dural foramina through which they exit the cranial cavity.

  15. A rat model of thrombosis in common carotid artery induced by implantable wireless light-emitting diode device.

    PubMed

    Yeh, Jih-Chao; Huang, Kuo-Lun; Hsiao, Yung-Chin; Hsu, Yu-Han; Lin, Yun-Han; Lou, Shyh-Liang; Lee, Tsong-Hai

    2014-01-01

    This work has developed a novel approach to form common carotid artery (CCA) thrombus in rats with a wireless implantable light-emitting diode (LED) device. The device mainly consists of an external controller and an internal LED assembly. The controller was responsible for wirelessly transmitting electrical power. The internal LED assembly served as an implant to receive the power and irradiate light on CCA. The thrombus formation was identified with animal sonography, 7 T magnetic resonance imaging, and histopathologic examination. The present study showed that a LED assembly implanted on the outer surface of CCA could induce acute occlusion with single irradiation with 6 mW/cm(2) LED for 4 h. If intermittent irradiation with 4.3-4.5 mW/cm(2) LED for 2 h was shut off for 30 min, then irradiation for another 2 h was applied; the thrombus was observed to grow gradually and was totally occluded at 7 days. Compared with the contralateral CCA without LED irradiation, the arterial endothelium in the LED-irradiated artery was discontinued. Our study has shown that, by adjusting the duration of irradiation and the power intensity of LED, it is possible to produce acute occlusion and progressive thrombosis, which can be used as an animal model for antithrombotic drug development.

  16. A Rat Model of Thrombosis in Common Carotid Artery Induced by Implantable Wireless Light-Emitting Diode Device

    PubMed Central

    Huang, Kuo-Lun; Hsiao, Yung-Chin; Lin, Yun-Han; Lou, Shyh-Liang; Lee, Tsong-Hai

    2014-01-01

    This work has developed a novel approach to form common carotid artery (CCA) thrombus in rats with a wireless implantable light-emitting diode (LED) device. The device mainly consists of an external controller and an internal LED assembly. The controller was responsible for wirelessly transmitting electrical power. The internal LED assembly served as an implant to receive the power and irradiate light on CCA. The thrombus formation was identified with animal sonography, 7T magnetic resonance imaging, and histopathologic examination. The present study showed that a LED assembly implanted on the outer surface of CCA could induce acute occlusion with single irradiation with 6 mW/cm2 LED for 4 h. If intermittent irradiation with 4.3–4.5 mW/cm2 LED for 2 h was shut off for 30 min, then irradiation for another 2 h was applied; the thrombus was observed to grow gradually and was totally occluded at 7 days. Compared with the contralateral CCA without LED irradiation, the arterial endothelium in the LED-irradiated artery was discontinued. Our study has shown that, by adjusting the duration of irradiation and the power intensity of LED, it is possible to produce acute occlusion and progressive thrombosis, which can be used as an animal model for antithrombotic drug development. PMID:25045695

  17. Frequency-Selective Response of the Tectorial Membrane in the Frog Basilar Papilla

    NASA Astrophysics Data System (ADS)

    Schoffelen, R. L. M.; Segenhout, J. M.; van Dijk, P.

    2009-02-01

    The frog's basilar papilla is a useful study object for cochlear mechanics, because of it's relatively simple anatomy and functionality. We investigated the displacement amplitudes of the basilar papilla's tectorial membrane in response to stimulation of the oval window at various frequencies within the auditory range of the Northern leopard frog. From our measurement data we find that the tectorial membrane exhibits a frequency selective response. The peak response was found to occur at 1500Hz in correspondence with known data for the response of auditory nerve fibers from the organ. From these data we conclude that mechanical tuning contributes significantly to the frequency selectivity of the frog's basilar papilla

  18. Gene Expression and MicroRNA Expression Analysis in Small Arteries of Spontaneously Hypertensive Rats. Evidence for ER Stress.

    PubMed

    Palao, Teresa; Swärd, Karl; Jongejan, Aldo; Moerland, Perry D; de Vos, Judith; van Weert, Angela; Arribas, Silvia M; Groma, Gergely; vanBavel, Ed; Bakker, Erik N T P

    2015-01-01

    Small arteries are known to develop functional and structural alterations in hypertension. However, the mechanisms of this remodeling are not fully understood. We hypothesized that altered gene expression is associated with the development of hypertension in mesenteric arteries of spontaneously hypertensive rats (SHR). Three sublines of SHR and normotensive Wistar Kyoto rats (WKY) were studied at 6 weeks and 5 months of age. MiRNA and mRNA microarray experiments were performed and analyzed with bioinformatical tools, including Ingenuity Pathway Analysis (IPA). Principal component analysis showed a clear separation in both miRNA and mRNA expression levels between both ages studied, demonstrating strong age-related changes in expression. At the miRNA level, IPA identified differences between SHR and WKY related to metabolic diseases, cellular growth, and proliferation. The mRNAs differentially expressed between SHR and WKY were related to metabolism, cellular movement and proliferation. The most strongly upregulated gene (9.2-fold) was thrombospondin 4 (Thbs4), a protein involved in the endoplasmic reticulum (ER) stress response that activates transcription factor 6α (ATF6α). ATF6α downstream targets were also differentially expressed in SHR vs. WKY. Differential expression of THBS4, the cleaved form of ATF6α, and two of its targets were further confirmed at the protein level by western blot. In summary, these data revealed a number of genes (n = 202) and miRNAs (n = 3) in mesenteric arteries of SHR that had not been related to hypertension previously. The most prominent of these, Thbs4, is related to vascular ER stress that is associated with hypertension.

  19. Acetylcholine- and sodium hydrosulfide-induced endothelium-dependent relaxation and hyperpolarization in cerebral vessels of global cerebral ischemia-reperfusion rat.

    PubMed

    Han, Jun; Chen, Zhi-Wu; He, Guo-Wei

    2013-01-01

    We investigated the effects of endothelium-derived hyperpolarizing factor (EDHF) and the role of hydrogen sulphide (H2S) in the cerebral vasorelaxation induced by acetylcholine (ACh) in global cerebral ischemia-reperfusion (CIR) rats. CIR was induced by occlusion of bilateral carotid and vertebral arteries. Isolated arterial segments from the cerebral basilar (CBA) and middle artery (MCA) of CIR rats were studied in a pressurized chamber. Transmembrane potential was recorded using glass microelectrodes to evaluate hyperpolarization. In the CIR CBAs and MCAs preconstricted by 30 mM KCl, ACh induced concentration-dependent vasorelaxation and hyperpolarization that were partially attenuated by NG-nitro-l-arginine methyl ester (l-NAME, 30 μM) and l-NAME plus indomethacin (10 μM). The residual responses were abolished by the H2S inhibitor dl-propargylglycine (PPG, 100 μM). The H2S donor NaHS and l-Cys, the substrate of endogenous H2S synthase, elicited similar responses to ACh and was inhibited by tetraethylamonine (1 mM) or PPG. ACh induces EDHF-mediated vasorelaxation and hyperpolarization in rat cerebral arteries. These responses are up-regulated by ischemia-reperfusion while NO-mediated responses are down-regulated. Further, the ACh-induced, EDHF-mediated relaxation, and hyperpolarization and the inhibition of these responses are similar to the H2S-induced responses, suggesting that H2S is a possible candidate for EDHF in rat cerebral vessels.

  20. Effects of baicalin on collagen Ι and collagen ΙΙΙ expression in pulmonary arteries of rats with hypoxic pulmonary hypertension

    PubMed Central

    LIU, PANPAN; YAN, SHUANGQUAN; CHEN, MAYUN; CHEN, ALI; YAO, DAN; XU, XIAOMEI; CAI, XUEDING; WANG, LIANGXING; HUANG, XIAOYING

    2015-01-01

    The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for

  1. An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Lau, Wing Hung; Kwan, Yiu Wa; Au, Alice Lai Shan; Cheung, Wui Hang

    2003-05-30

    The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via histamine N-methyl-transferase and diamine oxidase) on the vascular response of histamine, and the subtype(s) of histamine receptor present in the pulmonary artery (first branch, O.D. approximately 800 microm) of the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) (male, 22-26 weeks old). In phenylephrine (1 microM) pre-contracted preparations, histamine and 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT, a histamine H(1) receptor agonist) elicited a concentration-dependent relaxation, with a smaller magnitude recorded in SHR. Application of 10 microM S-[4-(N,N-dimethylamino)-butyl]isothiourea (SKF 91488, a selective histamine N-methyl-transferase inhibitor), but not aminoguanidine (100 microM, a diamine oxidase inhibitor), significantly attenuated histamine-induced relaxation. Clobenpropit (1 nM, a potent histamine H(3) receptor antagonist) "antagonised" the suppressive effect of SKF 91488 and histamine-evoked relaxation was restored. Endothelial denudation reduced histamine- and abolished HTMT-elicited relaxation. Dimaprit (a histamine H(2) receptor agonist) caused an endothelium-independent, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 microM, an adenylate cyclase inhibitor)-sensitive, concentration-dependent relaxation, with a similar magnitude in both strains of rat. Histamine-evoked relaxation was reversed into a further contraction (clobenpropit (10 nM)-sensitive) (with a greater magnitude occurred in the WKY rat) after blocking the histamine H(1) and H(2) receptors with diphenhydramine plus cimetidine (30 microM each). A similar further contraction

  2. Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bed

    PubMed Central

    McCulloch, Audrey I; Bottrill, Fiona E; Randall, Michael D; Robin Hiley, C

    1997-01-01

    We have used the isolated, buffer-perfused, mesenteric arterial bed of the rat (preconstricted with methoxamine or 60 mM K+) to characterize nitric oxide (NO)-independent vasorelaxation which is thought to be mediated by the endothelium-derived hyperpolarizing factor (EDHF).The muscarinic agonists carbachol, acetylcholine (ACh) and methacholine caused dose-related relaxations in preconstricted preparations with ED50 values of 0.18±0.04 nmol (n=8), 0.05±0.02 nmol (n=6) and 0.26±0.16 nmol (n=5), respectively. In the same preparations NG-nitro-L-arginine methyl ester (L-NAME, 100 μM) significantly (P<0.05) decreased the potency of all the agents (ED50 values in the presence of L-NAME: carbachol, 0.66±0.11 nmol; ACh, 0.28±0.10 nmol; methacholine, 1.97±1.01 nmol). The maximal relaxation to ACh was also significantly (P<0.05) reduced (from 85.3±0.9 to 73.2±3.7%) in the presence of L-NAME. The vasorelaxant effects of carbachol were not significantly altered by the cyclo-oxygenase inhibitor indomethacin (10 μM; n=4).The K+ channel blocker, tetraethylammonium (TEA, 10 mM) also significantly (P<0.001) reduced both the potency of carbachol (ED50=1.97±0.14 nmol in presence of TEA) and the maximum relaxation (Rmax=74.6±3.2% in presence of TEA, P<0.05, n=3). When TEA was added in the presence of L-NAME (n=4), there was a further significant (P<0.001) decrease in the potency of carbachol (ED50=22.4±13.5 nmol) relative to that in the presence of L-NAME alone, and Rmax was also significantly (P<0.05) reduced (74.6±4.2%). The ATP-sensitive K+ channel inhibitor, glibenclamide (10 μM), had no effect on carbachol-induced relaxation (n=9).High extracellular K+ (60 mM) significantly (P<0.01) reduced the potency of carbachol (n=5) by 5 fold (ED50: control, 0.16±0.04 nmol; high K+, 0.88±0.25 nmol) and the Rmax was also significantly (P<0.01) reduced (control, 83.4±2.7%; high K+, 40.3±9.2%). The residual vasorelaxation to carbachol in the

  3. Comparison of the effects of semicarbazide and {beta}-aminopropionitrile on the arterial extracellular matrix in the Brown Norway rat

    SciTech Connect

    Mercier, Nathalie; Kakou, Augustine; Challande, Pascal; Lacolley, Patrick; Osborne-Pellegrin, Mary

    2009-09-15

    To investigate a putative role for semicarbazide-sensitive amine oxidase (SSAO) in arterial extracellular matrix (ECM) organization, we compared arteries of growing Brown Norway (BN) rats after chronic administration of semicarbazide (SCZ) and {beta}-aminopropionitrile (BAPN), two inhibitors with different properties and relative specificities for SSAO and lysyl oxidase (LOX). The BN model is particularly well adapted to evaluating effects of toxic compounds on the arterial elastic network. We measured aortic LOX and SSAO activities and quantified several ECM parameters. After a pilot study comparing doses previously studied and testing for additivity, we studied low and high equimolar doses of SCZ and BAPN. Both compounds similarly inhibited LOX, whereas SCZ inhibited SSAO far more effectively than BAPN. Both decreased carotid wall rupture pressure, increased tail tendon collagen solubility, decreased aortic insoluble elastin (% dry weight) and dose-dependently increased defects in the internal elastic lamina of abdominal aorta, iliac and renal arteries. Our results suggest that either these effects are mediated by LOX inhibition, SCZ being slightly more effective than BAPN in our conditions, or SSAO acts similarly to and in synergy with LOX on ECM, the greater SCZ effect reflecting the simultaneous inhibition of both enzymes. However, the high SCZ dose increased aortic collagen and ECM proteins other than insoluble elastin markedly more than did equimolar BAPN, possibly revealing a specific effect of SSAO inhibition. To discriminate between the two above possibilities, and to demonstrate unequivocally a specific effect of SSAO inhibition on ECM formation or organization, we must await availability of more specific inhibitors.

  4. Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke.

    PubMed

    Coucha, Maha; Li, Weiguo; Johnson, Maribeth H; Fagan, Susan C; Ergul, Adviye

    2013-12-01

    The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N(ω)-nitro-l-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen-glucose deprivation experienced a similar loss of myogenic tone. Inhibition of peroxynitrite parent radicals significantly improved the myogenic tone. Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs

  5. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats

    PubMed Central

    Perez, Christina M.; Hazari, Mehdi S.; Ledbetter, Allen D.; Haykal-Coates, Najwa; Carll, Alex P.; Cascio, Wayne E.; Winsett, Darrell W.; Costa, Daniel L.; Farraj, Aimen K.

    2016-01-01

    Context Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. Objective We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Materials and methods Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Results Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Discussion and conclusion Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.) PMID:25600140

  6. Differential Effects of Long Term FTY720 Treatment on Endothelial versus Smooth Muscle Cell Signaling to S1P in Rat Mesenteric Arteries

    PubMed Central

    Hamidi Shishavan, Mahdi; Bidadkosh, Arash; Yazdani, Saleh; Lambooy, Sebastiaan; van den Born, Jacob; Buikema, Hendrik; Henning, Robert H.; Deelman, Leo E.

    2016-01-01

    The sphingosine-1-phosphate (S1P) analog FTY720 exerts pleiotropic effects on the cardiovascular system and causes down-regulation of S1P receptors. Myogenic constriction is an important mechanism regulating resistance vessel function and is known to be modulated by S1P. Here we investigated myogenic constriction and vascular function of mesenteric arteries of rats chronically treated with FTY720. Wistar rats received FTY720 1mg/kg/daily for six weeks. At termination, blood pressure was recorded and small mesenteric arteries collected for vascular studies in a perfusion set up. Myogenic constriction to increased intraluminal pressure was low, but a sub-threshold dose of S1P profoundly augmented myogenic constriction in arteries of both controls and animals chronically treated with FTY720. Interestingly, endothelial denudation blocked the response to S1P in arteries of FTY720-treated animals, but not in control rats. In acute experiments, presence of FTY720 significantly augmented the contractile response to S1P, an effect that was partially abolished after the inhibition of cyclooxygenase (COX-)-derived prostaglandins. FTY720 down regulated S1P1 but not S1P2 in renal resistance arteries and in cultured human endothelial cells. This study therefore demonstrates the endothelium is able to compensate for the complete loss of responsiveness of the smooth muscle layer to S1P after long term FTY720 treatment through a mechanism that most likely involves enhanced production of contractile prostaglandins by the endothelium. PMID:27583547

  7. Aortic and Carotid Arterial Stiffness and Epigenetic Regulator Gene Expression Changes Precede Blood Pressure Rise in Stroke-Prone Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Herrera, Victoria L.; Decano, Julius L.; Giordano, Nicholas; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2014-01-01

    Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation. PMID:25229245

  8. Basilar membrane vibration is not involved in the reverse propagation of otoacoustic emissions.

    PubMed

    He, W; Ren, T

    2013-01-01

    To understand how the inner ear-generated sound, i.e., otoacoustic emission, exits the cochlea, we created a sound source electrically in the second turn and measured basilar membrane vibrations at two longitudinal locations in the first turn in living gerbil cochleae using a laser interferometer. For a given longitudinal location, electrically evoked basilar membrane vibrations showed the same tuning and phase lag as those induced by sounds. For a given frequency, the phase measured at a basal location led that at a more apical location, indicating that either an electrical or an acoustical stimulus evoked a forward travelling wave. Under postmortem conditions, the electrically evoked emissions showed no significant change while the basilar membrane vibration nearly disappeared. The current data indicate that basilar membrane vibration was not involved in the backward propagation of otoacoustic emissions and that sounds exit the cochlea probably through alternative media, such as cochlear fluids.

  9. Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage Associated with Bilateral Common Carotid Artery Occlusion

    PubMed Central

    Meguro, T.; Tanabe, T.; Muraoka, K.; Terada, K.; Hirotsune, N.; Nishino, S.

    2008-01-01

    Summary Cases of aneurysm associated with the occlusion of both common carotid arteries are very rare. We present a case of ruptured aneurysms of the basilar bifurcation and posterior cerebral artery coexisting with bilateral common carotid artery occlusion, successfully treated by endovascular coil embolization with a double-balloon remodeling technique. Finally, we review the literature. A 62-year-old woman presented with severe headache; a computed tomography scan demonstrated subarachnoid hemorrhage. Angiography revealed that the bilateral common carotid arteries were occluded. The muscle branches of the vertebral arteries had anastomosed to the bilateral external carotid arteries. Bilateral posterior communicating arteries had developed and supplied the bilateral internal carotid arteries. Two aneurysms (a saccular aneurysm of the P1 portion of the left posterior cerebral artery and a wide-necked aneurysm of the basilar bifurcation) were also observed. Endovascular embolization of the aneurysms was successfully performed using a double-balloon remodeling technique. The patient made a full recovery after treatment, and the aneurysms remained obliterated 12 months after embolization. We believe that this is the first report of ruptured aneurysms associated with bilateral common carotid artery occlusion successfully treated by endovascular coiling. The double-balloon remodeling technique was useful for treatment of wide-necked basilar bifurcation aneurysm. PMID:20557745

  10. Anterior and posterior inferior cerebellar artery infarction with sudden deafness and vertigo.

    PubMed

    Murakami, Takenobu; Nakayasu, Hiroyuki; Doi, Mitsuru; Fukada, Yasuyo; Hayashi, Miwa; Suzuki, Takeo; Takeuchi, Yuichi; Nakashima, Kenji

    2006-12-01

    We report a patient with anterior and posterior inferior cerebellar artery infarction, which manifested as profound deafness, transient vertigo, and minimal cerebellar signs. We suspect that ischaemia of the left internal auditory artery, which originates from the anterior inferior cerebellar artery, caused the deafness and transient vertigo. A small lesion in the middle cerebellar peduncle in the anterior inferior cerebellar artery territory and no lesion in the dentate nucleus in the posterior inferior cerebellar artery territory are thought to explain the minimal cerebellar signs despite the relatively large size of the infarction. Thus a relatively large infarction of the vertebral-basilar territory can manifest as sudden deafness with vertigo. Neuroimaging, including magnetic resonance imaging, is strongly recommended for patients with sudden deafness and vertigo to exclude infarction of the vertebral-basilar artery territory.

  11. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

    PubMed Central

    Ghosh, P; Bitsanis, D; Ghebremeskel, K; Crawford, M A; Poston, L

    2001-01-01

    Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. PMID:11410637

  12. Excess Salt Increases Infarct Size Produced by Photothrombotic Distal Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

    PubMed Central

    Yao, Hiroshi; Nabika, Toru

    2014-01-01

    Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline) or water, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF), determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p = 0.002), while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels) were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats. PMID:24816928

  13. Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes.

    PubMed

    Villalobos-Molina, R; Ibarra, M

    1996-03-18

    Alpha 1-Adrenoceptor subtypes mediating contraction in carotid, aorta, mesenteric and caudal arteries from both Wistar Kyoto (WKY) normotensive and spontaneously hypertensive (SHR) rats were investigated by using the alpha 1A-adrenoceptor agonist methoxamine and antagonized with selective, competitive antagonists WB-4101, 5-methyl urapidil or BMY 7378 (8-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)decane -7,9-dione dihydrochloride). Isometric tension changes were recorded after methoxamine addition to the arterial rings, and the effects of the antagonists determined. All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries. Due to the high pA2 values for 5-methyl urapidil and WB-4101 and the low values for BMY 7378 we conclude that the tail artery expresses the alpha 1A and not the alpha 1B subtype. No differences were found between both strains of rats, suggesting that hypertension does not modify the alpha 1-adrenoceptors in conductance arteries. PMID:8846824

  14. Potential Role of Axonal Chemorepellent Slit2 in Modulating Adventitial Inflammation in a Rat Carotid Artery Balloon Injury Model.

    PubMed

    Liu, Dong; Xiao, Yan; Subramanian, Romesh R; Okamoto, Ei-Ichi; Wilcox, Josiah N; Anderson, Leonard; De Leon, Hector

    2016-05-01

    Leukocyte infiltration of adventitial and perivascular tissues is an early event in the development of vascular remodeling after injury. We investigated whether Slit/Robo-an axonal chemorepellent system in vertebrate and invertebrate development-is activated during the inflammatory phase that follows endothelial denudation. Using the rat carotid artery model of angioplasty, we conducted a time course analysis of mRNAs encoding Slit ligands (Slit2 and Slit3) and Robo receptors (Robo1, Robo2, and Robo4), as well as proinflammatory cell adhesion molecule (CAM) genes. Adventitial inflammatory cells were counted in immunostained arterial sections. E-selectin, vascular CAM-1, and intercellular CAM-1 were upregulated 2-3 hours after injury, followed by infiltration of neutrophils and monocytes as evidenced by real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. Slit2, Slit3, and Robo genes exhibited no expression changes at 3 hours; however, they were markedly upregulated 1 day after angioplasty. Intercellular CAM-1 expression was reduced by 50%, and the number of adventitial neutrophils decreased by >75% 1 day after angioplasty. Slit2 has been shown to be a potent chemorepelent of leukocytes, endothelial cells, and smooth muscle cells. Thus, we decided to further investigate the localization of Slit2 in injured vessels. Immunohistochemical stainings revealed the presence of Slit2 within the vessel wall and in the perivascular vasa vasorum of naive and injured arteries. Double immunohistochemical analyses showed that infiltrating monocytes expressed Slit2 in the perivascular and adventitial tissues of injured arteries 1 and 3 days postangioplasty. In addition, recombinant full-length Slit2 and Slit2-N/1118, an N-terminal fragment of Slit2, inhibited stromal cell-derived factor 1-mediated migration of circulating rat peripheral blood mononuclear cells. In summary, adventitial activation of CAM genes and neutrophil infiltration preceded

  15. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels.

    PubMed

    Peixoto-Neves, Dieniffer; Leal-Cardoso, Jose Henrique; Jaggar, Jonathan H

    2014-11-01

    Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca) currents, when using Ba as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca currents involved pore block, a hyperpolarizing shift (∼-10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivation rate. In summary, our data indicate that eugenol dilates cerebral arteries by means of multimodal inhibition of voltage-dependent Ca channels.

  16. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels

    PubMed Central

    Peixoto-Neves, Dieniffer; Leal-Cardoso, Jose Henrique; Jaggar, Jonathan H.

    2014-01-01

    Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K+) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca2+) currents, when using Ba2+ as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca2+ currents involved pore block, a hyperpolarizing shift ( ~−10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivaiton rate. In summary, our data indicate that eugenol dilates cerebral arteries via multi-modal inhibition of voltage-dependent Ca2+ channels. PMID:24921632

  17. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels.

    PubMed

    Peixoto-Neves, Dieniffer; Leal-Cardoso, Jose Henrique; Jaggar, Jonathan H

    2014-11-01

    Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca) currents, when using Ba as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca currents involved pore block, a hyperpolarizing shift (∼-10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivation rate. In summary, our data indicate that eugenol dilates cerebral arteries by means of multimodal inhibition of voltage-dependent Ca channels. PMID:24921632

  18. Activation of two sites by adenosine receptor agonists to cause relaxation in rat isolated mesenteric artery

    PubMed Central

    Prentice, D J; Payne, S L; Hourani, S M O

    1997-01-01

    In this study we have characterized the receptor(s) in the rat mesenteric artery mediating relaxant responses to adenosine and a number of adenosine analogues, N6 -R-phenylisopropyladenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-(3-iodo-benzyl)-adenosine-5′-N-methyluronamide (IB-MECA) and 5′-N-ethylcarboxamidoadenosine (NECA), by use of the non-selective antagonist 8-sulphophenyltheophylline (8-SPT) and the A2A selective ligands 2-[p-(2-carbonylethyl)-phenylethylamino]-5′-N-ethylcarboxamidoadenosine (CGS 21680) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]-triazin-5-ylamino]ethyl) phenol (ZM 241385). We have also studied the effects of endothelial removal and uptake inhibition by nitrobenzylthioinosine (NBTI) and the effects of the A3 receptor antagonist 1,3-dipropyl-8-(4-acrylate)phenylxanthine (BWA1433).Adenosine, NECA, CPA and R-PIA all elicited relaxant responses in tissues precontracted with phenylephrine (1 μM) with the following potency order: NECA>R-PIA>adenosine=CPA. However, E/[A] curves to NECA were biphasic. CGS 21680 was inactive at concentrations up to 30 μM and IB-MECA elicited relaxant responses which were resistant to blockade by 8-SPT and BWA1433 (100 μM).Removal of the endothelium produced a small but significant decrease in the asymptote of the high potency phase of E/[A] curves to NECA with no change in p[A]50. E/[A] curves to adenosine were not altered by removal of the endothelium. However, there were small rightward shifts of E/[A] curves to CPA and R-PIA in the absence of endothelium.Inhibition of uptake by NBTI (1 μM) had no effect on E/[A] curves to NECA, CPA or R-PIA, but E/[A] curves to adenosine were significantly left-shifted in the presence of NBTI.8-SPT (10–100 μM) caused significant rightward shifts of the high potency phase of the E/[A] curves to NECA (pA2=5.63±0.26). The second phase of the concentration-response curve to NECA appeared to be resistant to blockade by 8-SPT, as were E

  19. Rat Middle Cerebral Artery Occlusion Is Not a Suitable Model for the Study of Stroke-Induced Spontaneous Infections

    PubMed Central

    Campos-Martorell, Mireia; Hernández-Guillamón, Mar; Rosell, Anna; Gomis, Javier; Salat, David; García-Bonilla, Lidia; Montaner, Joan

    2014-01-01

    Background Infections related to stroke-induced immunodepression are an important complication causing a high rate of death in patients. Several experimental studies in mouse stroke models have described this process but it has never been tested in other species such as rats. Methods Our study focused on the appearance of secondary systemic and pulmonary infections in ischemic rats, comparing with sham and naive animals. For that purpose, male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) or to transient MCAO (tMCAO) inserting a nylon filament. Forty-eight hours after ischemia, blood and lung samples were evaluated. Results In eMCAO set, ischemic rats showed a significant decrease in blood-peripheral lymphocytes (naive = 58.8±18.1%, ischemic = 22.9±16.4%) together with an increase in polymorphonuclears (PMNs) (naive = 29.2±14.7%, ischemic = 71.7±19.5%), while no change in monocytes was observed. The increase in PMNs counts was positively correlated with worse neurological outcome 48 hours after eMCAO (r = 0.55, p = 0.043). However, sham animals showed similar changes in peripheral leukocytes as those seen in ischemic rats (lymphocytes: 40.1±19.7%; PMNs: 51.7±19.2%). Analysis of bacteriological lung growth showed clear differences between naive (0±0 CFU/mL; log10) and both sham (3.9±2.5 CFU/mL; log10) and ischemic (4.3±2.9 CFU/mL; log10) groups. Additionally, naive animals presented non-pathological lung histology, while both sham and ischemic showed congestion, edema or hemorrhage. Concordant results were found in the second set of animals submitted to a tMCAO. Conclusions Inflammatory and infection changes in Wistar rats subjected to MCAO models may be attributed not only to the brain ischemic injury but to the surgical aggression and/or anaesthetic stress. Consequently, we suggest that stroke-induced immunodepression in ischemic experimental models should be interpreted with caution in further

  20. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  1. Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model.

    PubMed

    Guan, Siyu; Tang, Qizhu; Liu, Wenwei; Zhu, Rui; Li, Bin

    2014-12-01

    Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti-inflammatory and anti-oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet-derived growth factor (PDGF)-BB- stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF-BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF-BB-induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF-κB p65 in PDGF-BB-stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon-injured rat carotid arteries. Serum levels of TNF-α and IL-6 in nobiletin-treated rats were decreased. These results indicated that nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.

  2. The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

    PubMed

    Darios, Emma S; Winner, Brittany M; Charvat, Trevor; Krasinksi, Antoni; Punna, Sreenivas; Watts, Stephanie W

    2016-08-01

    The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 μM)-amplified EFS-induced contraction in arteries (with and without PVAT) was blocked by CCX832 and the α-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nerve-mediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the well-appreciated role of the sympathetic nervous system in blood pressure control. PMID:27371688

  3. Pressure-dependent contribution of Rho kinase-mediated calcium sensitization in serotonin-evoked vasoconstriction of rat cerebral arteries.

    PubMed

    El-Yazbi, Ahmed F; Johnson, Rosalyn P; Walsh, Emma J; Takeya, Kosuke; Walsh, Michael P; Cole, William C

    2010-05-15

    Our understanding of the cellular signalling mechanisms contributing to agonist-induced constriction is almost exclusively based on the study of conduit arteries. Resistance arteries/arterioles have received less attention as standard biochemical approaches lack the necessary sensitivity to permit quantification of phosphoprotein levels in these small vessels. Here, we have employed a novel, highly sensitive Western blotting method to assess: (1) the contribution of Ca(2+) sensitization mediated by phosphorylation of myosin light chain phosphatase targeting subunit 1 (MYPT1) and the 17 kDa PKC-potentiated protein phosphatase 1 inhibitor protein (CPI-17) to serotonin (5-HT)-induced constriction of rat middle cerebral arteries, and (2) whether there is any interplay between pressure-induced myogenic and agonist-induced mechanisms of vasoconstriction. Arterial diameter and levels of MYPT1 (T697 and T855), CPI-17 and 20 kDa myosin light chain subunit (LC(20)) phosphorylation were determined following treatment with 5-HT (1 micromol l(1)) at 10 or 60 mmHg in the absence and presence of H1152 or GF109203X to suppress the activity of Rho-associated kinase (ROK) and protein kinase C (PKC), respectively. Although H1152 and GF109203X suppressed 5-HT-induced constriction and reduced phospho-LC(20) content at 10 mmHg, we failed to detect any increase in MYPT1 or CPI-17 phosphorylation. In contrast, an increase in MYPT1-T697 and MYPT1-T855 phosphorylation, but not phospho-CPI-17 content, was apparent at 60 mmHg following exposure to 5-HT, and the phosphorylation of both MYPT1 sites was sensitive to H1152 inhibition of ROK. The involvement of MYPT1 phosphorylation in the response to 5-HT at 60 mmHg was not dependent on force generation per se, as inhibition of cross-bridge cycling with blebbistatin (10 micromol l(1)) did not affect phosphoprotein content. Taken together, the data indicate that Ca(2+) sensitization owing to ROK-mediated phosphorylation of MYPT1 contributes to 5

  4. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  5. Heart function in magnetic resonance imaging and the mesenteric artery reactivity in rats receiving lead-contaminated drinking water.

    PubMed

    Skoczynska, A; Skórka, T; Wojakowska, A; Nowacki, D; Turczyn, B; Poręba, R; Tyrankiewicz, U; Byk, K; Szuba, A

    2014-05-01

    The aim of this study was to evaluate the effect of lead (Pb)-contaminated drinking water on magnetic resonance imaging (MRI)-estimated cardiac function, vascular reactivity, and serum lipids in rats. For 3 months, male Wistar rats, aged 4-6 weeks, were given drinking water with the addition of lead acetate at a concentration of 100 ppm Pb (10 rats) or water free from Pb (8 control rats). The cardiac MRI was performed at rest and under β-adrenergic stimulation on a 4.7 T scanner using electrocardiogram-triggered gradient echo (FLASH) cine sequence. After 1-2 weeks of the MRI test, experiments were performed ex vivo. After stabilization of perfusion pressure (PP), norepinephrine at doses from 0.01 to 5.0 μg was dissolved in Krebs solution, injected in a volume of 100 μl, and next infused at a concentration of 0.5 μg/ml into the isolated mesenteric artery. In this manner, preconstricted mesenteric bed was used to determine PP changes induced by acetylcholine, given at doses from 0.05 to 5.0 μg, before and during the infusion of nitric oxide synthase inhibitor (1.0 μg/ml). At the end, dobutamine (5 mg), followed by potassium chloride (10.5 mg), was injected. Lipid levels were determined enzymatically, blood Pb level was measured by the atomic absorption spectrophotometer. This study showed that Pb impairs the left ventricular systolic and diastolic function. Pb-induced changes in response to resistance of vessels to vasoactive agents may be secondary to the reduced left ventricular ejection fraction. The high-density lipoprotein subfraction 2 (HDL2) is involved in the cardiovascular effect of Pb.

  6. Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

    PubMed Central

    Sánchez, Ana; Contreras, Cristina; Martínez, María Pilar; Climent, Belén; Benedito, Sara; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

    2012-01-01

    Objective Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes. Methods and Results Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR). Blockade of NO synthase (NOS) inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4) restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH) reduced neural relaxations in arteries from LZR but not OZR. The NO donor SNAP induced decreases in intracellular calcium that were impaired in arteries from OZR compared to controls. Conclusions The present study demonstrates nitrergic dysfunction and impaired neural NO signalling due to oxidative stress and nNOS uncoupling in penile arteries under conditions of insulin resistance. This

  7. [The effect of low-intensity red and infrared laser radiation on the rat arterial and deoxygenated blood].

    PubMed

    Timoshenko, T E; Dvoretskiĭ, D P

    2010-10-01

    In vitro experiments the effect of low-intensity red or near-infrared laser irradiation on the blood samples (1.5 ml from abdominal aorta of Wistar rats) were studied. The diode laser light (lambda = 650 nm or 808 nm, power density 15.6 mW/cm2, duration 15 min) were used. In some experiments the deoxygenated blood as object for comparison with arterial blood was chosen. Under red laser irradiation we observed a significant increase of average volume of erythrocytes as well as mean amount of free (disaggregated) leukocytes especially in case of the deoxygenated blood. At the same time the concentration of Ca2+ and Na+ were decreased. The effects of infrared laser irradiation on indices mentioned above were not significant. We believe that red low-intensity laser irradiation on the blood is an important factor for theological properties in the field of microcirculation.

  8. Involvement of voltage-dependent potassium channels in the EDHF-mediated relaxation of rat hepatic artery

    PubMed Central

    Zygmunt, Peter M; Edwards, Gillian; Weston, Arthur H; Larsson, Bengt; Högestätt, Edward D

    1997-01-01

    In the rat hepatic artery, the acetylcholine-induced relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF) is abolished by a combination of apamin and charybdotoxin, inhibitors of small (SKCa) and large (BKCa) conductance calcium-sensitive potassium (K)-channels, respectively, but not by each toxin alone. The selective BKCa inhibitor iberiotoxin cannot replace charybdotoxin in this combination. Since delayed rectifier K-channels (KV) represent another target for charybdotoxin, we explored the possible involvement of KV in EDHF-mediated relaxation in this artery. The KV inhibitors, agitoxin-2 (0.3 μM), kaliotoxin (0.3 μM), β-dendrotoxin (0.3 μM), dofetilide (1 μM) and terikalant (10 μM), each in combination with apamin (0.3 μM) had no effect on the EDHF-mediated relaxation induced by acetylcholine in the presence of Nω-nitro-L-arginine (0.3 mM) and indomethacin (10 μM), inhibitors of nitric oxide (NO) synthase and cyclo-oxygenase, respectively (n=2–3). Although the KV inhibitor margatoxin (0.3 μM) was also without effect (n=5), the combination of margatoxin and apamin produced a small inhibition of the response (pEC50 and Emax values were 7.5±0.0 and 95±1% in the absence and 7.0±0.1 and 81±6% in the presence of margatoxin plus apamin, respectively; n=6; P<0.05). Ciclazindol (10 μM) partially inhibited the EDHF-mediated relaxation by shifting the acetylcholine-concentration-response curve 12 fold to the right (n=6; P<0.05) and abolished the response when combined with apamin (0.3 μM; n=6). This combination did not inhibit acetylcholine-induced relaxations mediated by endothelium-derived NO (n=5). A 4-aminopyridine-sensitive delayed rectifier current (IK(V)) was identified in freshly-isolated single smooth muscle cells from rat hepatic artery. None of the cells displayed a rapidly-activating and -inactivating A-type current. Neither charybdotoxin (0.3 μM; n=3) nor ciclazindol (10 μM; n=5), alone or in

  9. The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion-induced arrhythmias in anaesthetized rats.

    PubMed Central

    Fagbemi, O.; Kane, K. A.; McDonald, F. M.; Parratt, J. R.; Rothaul, A. L.

    1984-01-01

    In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg-1), prenylamine (0.5 mg kg-1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg-1) and cinnarizine (0.25, 0.5 and 1.0 mg kg-1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg-1), prenylamine (5 mg kg-1) and flunarizine (2.5 mg kg-1) did not afford a similar protection and mortality was increased to or above control values. Death was due in prenylamine-treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia-induced arrhythmias, this protective effect may be limited to a narrow concentration range. PMID:6487894

  10. Effect of short-term organoid culture on the pharmaco-mechanical properties of rat extra- and intrapulmonary arteries.

    PubMed

    Guibert, Christelle; Savineau, Jean Pierre; Crevel, Huguette; Marthan, Roger; Rousseau, Eric

    2005-11-01

    1 Organoid cultured explants from differentiated tissues have gained renewed interest in the undertaking of physiological and pharmacological studies. In the work herein, we examined the pharmaco-mechanical properties of an in vitro model consisting of organoid cultured rings derived from rat extra- and intrapulmonary arteries, over a period of 4 days in culture. 2 Mechanical changes were quantified using isometric tension measurements on both fresh and cultured pulmonary arterial tissues, with experiments performed in the presence or absence of 10% foetal calf serum. Conventional histochemical and immunofluorescent stainings were also performed to assess tissue structure integrity and apoptosis. 3 The explants developed spontaneous rhythmic contractions (SRC) in approximately half of the vessels. SRC amplitude and time course were modified by conditions and agents acting on membrane potential (high-potassium solutions--levcromakalim, a potassium channel opener), while nitrendipine, an L-type calcium channel blocker, suppressed SRC. 4 Cultured explants also developed a hyper-reactivity to high potassium challenges (10-40 mM). Whereas contraction to serotonin (5-HT) was enhanced in intrapulmonary arteries, contraction to endothelin-1 remained unchanged after 4 days of culture. Serum did not alter contractile properties during the culture period. 5 Endothelial-dependent relaxation was maintained in response to A23187 500 microM, but was abolished in response to 10 microM carbamylcholine. 6 Histological and immuno-histological analyses revealed the absence of hypertrophied vascular wall or apoptosis. 7 In conclusion, the contractile phenotype as well as tissue structure integrity of organoid explants remain essentially intact during short-term culture, making this model suitable for pharmaco-genomic studies. PMID:16151441

  11. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension.

    PubMed

    Fowler, Ewan D; Benoist, David; Drinkhill, Mark J; Stones, Rachel; Helmes, Michiel; Wüst, Rob C I; Stienen, Ger J M; Steele, Derek S; White, Ed

    2015-09-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control animals. In vivo right ventricular diastolic pressure-volume relationships were measured in anesthetized animals; diastolic force-length relationships in single enzymatically dissociated myocytes and myocardial creatine kinase levels by Western blot. We observed diastolic dysfunction in right ventricular failure indicated by significantly steeper diastolic pressure-volume relationships in vivo and diastolic force-length relationships in single myocytes. There was a significant reduction in creatine kinase protein expression in failing right ventricle. Dysfunction also manifested as a shorter diastolic sarcomere length in failing myocytes. This was associated with a Ca(2+)-independent mechanism that was sensitive to cross-bridge cycling inhibition. In saponin-skinned failing myocytes, addition of exogenous creatine kinase significantly lengthened sarcomeres, while in intact healthy myocytes, inhibition of creatine kinase significantly shortened sarcomeres. Creatine kinase inhibition also changed the relatively flat contraction amplitude-stimulation frequency relationship of healthy myocytes into a steeply negative, failing phenotype. Decreased creatine kinase expression leads to diastolic dysfunction. We propose that this is via local reduction in ATP:ADP ratio and thus to Ca(2+)-independent force production and diastolic sarcomere shortening. Creatine kinase inhibition also mimics a definitive characteristic of heart failure, the inability to respond to increased demand. Novel therapies for pulmonary artery hypertension are needed. Our data suggest that cardiac energetics would be a potential ventricular therapeutic target.

  12. Endothelial-derived hyperpolarization factor (EDHF) contributes to PlGF-induced dilation of mesenteric resistance arteries from pregnant rats.

    PubMed

    Mandalà, Maurizio; Gokina, Natalia; Barron, Carolyn; Osol, George

    2012-01-01

    The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 ± 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 ± 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SK(Ca) (apamin) and BK(Ca) (iberiotoxin) but not IK(Ca) (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SK(Ca) channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BK(Ca) channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre- eclampsia.

  13. Virtual Treatment of Basilar Aneurysms Using Shape Memory Polymer Foam

    NASA Astrophysics Data System (ADS)

    Ortega, J. M.; Hartman, J.; Rodriguez, J. N.; Maitland, D. J.

    2012-11-01

    Numerical simulations are performed on patient-specific basilar aneurysms that are treated with shape memory polymer (SMP) foam. In order to assess the post-treatment hemodynamics, two modeling approaches are employed. In the first, the foam geometry is obtained from a micro-CT scan and the pulsatile blood flow within the foam is simulated for both Newtonian and non-Newtonian viscosity models. In the second, the foam is represented as a porous media continuum, which has permeability properties that are determined by computing the pressure gradient through the foam geometry over a range of flow speeds comparable to those of in vivo conditions. Virtual angiography and additional post-processing demonstrate that the SMP foam significantly reduces the blood flow speed within the treated aneurysms, while eliminating the high-frequency velocity fluctuations that are present prior to treatment. A prediction of the initial locations of thrombus formation throughout the SMP foam is obtained by means of a low fidelity thrombosis model that is based upon the residence time and shear rate of blood. The two modeling approaches capture similar qualitative trends for the initial locations of thrombus within the SMP foam.

  14. The SPECT imaging shows the accumulation of neural progenitor cells into internal organs after systemic administration in middle cerebral artery occlusion rats.

    PubMed

    Lappalainen, Riikka S; Narkilahti, Susanna; Huhtala, Tuulia; Liimatainen, Timo; Suuronen, Tiina; Närvänen, Ale; Suuronen, Riitta; Hovatta, Outi; Jolkkonen, Jukka

    2008-08-01

    The regenerative potential of stem cells from various sources has been under intense investigation in the experimental models of cerebral ischemia. To end up with a restorative therapeutic treatment, it is crucial to get the cell transplants to the site of injury. Here, we evaluated the feasibility of small animal SPECT/CT in assessing the definite accumulation of (111)In-oxine-labeled human embryonic stem (ES) cell-derived neural progenitors and rat hippocampal progenitors after intravenous or intra-arterial administration (femoral vein vs. common carotid artery) in middle cerebral artery occlusion (MCAO) and sham-operated rats. Cell detection was carried out immediately and 24h after the infusion using a SPECT/CT device. The results showed that after intravenous injections both cell types accumulated primarily into internal organs, instead of brain. In contrast, after intra-arterial injection, a weak signal was detected in the ischemic hemisphere. Additional studies showed that the detection sensitivity of SPECT/CT device was approximately 1000 (111)In-oxine-labeled cells and labeling did not affect the cell viability. In conclusion, a small animal SPECT is powerful technique to study the whole body biodistribution of cell-based therapies. Our data showed that intravenous administration is not an optimal route to deliver neural progenitor cell-containing transplants into the brain after MCAO in rats. PMID:18572314

  15. Alteration in contractile G-protein coupled receptor expression by moist snus and nicotine in rat cerebral arteries

    SciTech Connect

    Sandhu, Hardip; Xu Cangbao; Edvinsson, Lars

    2011-04-15

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET{sub B}, serotonin 5-HT{sub 1B}, and thromboxane A{sub 2} TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24 h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine was kept at plasma level of snus users (25 ng nicotine/ml). A high dose (250 ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c, 5-HT{sub 1B} receptor agonist 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET{sub B}, 5-HT{sub 1B}, and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25 ng nicotine/ml) lowered the 5-HT{sub 1B} receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250 ng nicotine/ml) increased the ET{sub B} receptor-mediated contraction. The combined 5-HT{sub 1B} and 5-HT{sub 2A} receptor-mediated contraction was increased, and both the 5-CT and TxA2 induced contractions were left-ward shifted by WSS, DSS, or

  16. Effects of 4-Week Hindlimb Unweighting with and without 1H/Day Standing on Myogenic-Tone and Vasoconstrictor Responses of Mesenteric Arteries in Rats

    NASA Astrophysics Data System (ADS)

    Lin, Le-Jian; Bao, Jun-Xiang; Bai, Yun-Gang; Zhang, Li-Fan; Ma, Jin

    2008-06-01

    This study was designed to determine the effects of 4-week hindlimd unweighting (HU) with and without 1h/day standing (STD) on myotonic-tone and vasoconstrictor responses of rats mesenteric resistance arteries. Male Sprague-Dawley rats were subjected to 4-week hindlimb-unweighting to simulate cardiovascular deconditioning due to microgravity, 1h/day standing as the countermeasure. The diameter of isolated mesenteric resistance artery (diameter from 180-220μm) were recorded with Pressure myograph system in both Physiology salt solution (Da) and calcium-free Physiology salt solution (Dp), the myogenic-tone were obtained from (Dp-Da)/Dp*100%. The responses of these arteries to vasoconstrictors Phenylephrine were also detected. Results showed that 1) The myogenic tone of arteries was significantly attenuated by 4-week hindlimb-unweighting in HU group compared to control (CON) group(P<0.05); With 1h/day standing, the attenuated myogenic tone was recovered completely (P<0.05). 2) The vasoconstrictor responses of arteries to PE was decreased by 4-week hindlimb unweighting, and 1h/day standing can also prevent the attenuation (P<0.05). These results indicated that the myogenic tone and vasoconstrictor responses of rats mesenteric arteries were significantly attenuated by 4-week hindlimb-unweighting, 1h/d standing can prevent the attenuation completely, which could give us a better understanding of the underlying mechanism of orthostatic-intolerance post-flight and can also provide us new countermeasures to avoid it.

  17. Monocytes are Essential for the Neuroprotective Effect of Human Cord Blood Cells Following Middle Cerebral Artery Occlusion in Rat

    PubMed Central

    Womble, T. A.; Green, S.; Shahaduzzaman, M.; Grieco, J.; Sanberg, P. R.; Pennypacker, K. R.; Willing, A. E.

    2014-01-01

    Systemic administration of human umbilical cord blood (HUCB) mononuclear cells (MNC) following middle cerebral artery occlusion (MCAO) in the rat reduces infarct size and, more importantly, restores motor function. The HUCB cell preparation is composed of immature T-cells, B-cells, monocytes and stem cells. In this study we examined whether the beneficial effects of HUCB injection were attributable to one of these cell types. Male Sprague Dawley rats underwent permanent MCAO followed 48 hours later by intravenous administration of HUCB MNC preparations depleted of either CD14+ monocytes, CD133+ stem cells, CD2+ T-cells or CD19+ B cells. Motor function was measured prior to MCAO and 30 days post-stroke. When CD14+ monocytes were depleted from the HUCB MNC, activity and motor asymmetry were similar to the MCAO only treated animals. Monocyte depletion prevented HUCB cell treatment from reducing infarct size while monocyte enrichment was sufficient to reduce infarct size. Administration of monocyte-depleted HUCB cells did not suppress Iba1 labeling of microglia in the infarcted area relative to treatment with the whole HUCB preparation. These data demonstrate that the HUCB monocytes provide the majority of the efficacy in reducing infarct volume and promoting functional recovery. PMID:24472845

  18. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    PubMed Central

    2010-01-01

    Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

  19. Effect of early diabetes on the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of Wistar Kyoto and spontaneously hypertensive rats.

    PubMed

    Edith-Rodriguez, Jessica; Resendiz-Albor, Aldo Arturo; Arciniega-Martinez, Ivonne Maciel; Campos-Rodriguez, Rafael; Hong, Enrique; Huang, Fengyang; Villafaña, Santiago

    2013-01-01

    Hypertension and diabetes have been related to noradrenergic system impairment, especially to the response mediated by alpha-1 receptors. The aim of this work was to investigate possible changes in the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of Wistar Kyoto and spontaneously hypertensive rats after 4 weeks of the onset of diabetes. Our results suggest that early diabetes modifies the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of both WKY and SHR strains in a different way.

  20. Reduced nitric oxide-mediated relaxation and endothelial nitric oxide synthase expression in the tail arteries of streptozotocin-induced diabetic rats.

    PubMed

    Mokhtar, Siti Safiah; Vanhoutte, Paul M; Leung, Susan Wai Sum; Suppian, Rapeah; Yusof, Mohd Imran; Rasool, Aida Hanum Ghulam

    2016-02-15

    Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 ± 2.48% versus 85.05 ± 3.15%). Incubation with the combination of non-selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 ± 5.84% versus 68.39 ± 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 ± 6.74% versus 34.16 ± 4.59%) (prostacyclin; 15.85 ± 3.27% versus 17.23 ± 3.75%)]. Endothelium-independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction.

  1. Comparison of the Efficiencies of Buffers Containing Ankaferd and Chitosan on Hemostasis in an Experimental Rat Model with Femoral Artery Bleeding

    PubMed Central

    Abacıoğlu, Serkan; Aydın, Kemal; Büyükcam, Fatih; Kaya, Ural; Işık, Bahattin; Karakılıç, Muhammed Evvah

    2016-01-01

    Objective: In the first assessment of trauma patients with major vascular injuries, we need effective and rapid-acting homeostatic materials. In this study we compare the efficiencies of Ankaferd Blood Stopper® and a chitosan linear polymer (Celox®) in an experimental rat model with femoral artery bleeding. Materials and Methods: Thirty male Wistar albino rats weighing 200-250 g were divided into 3 groups: control, Ankaferd, and chitosan. The femoral artery and vein were visualized and bleeding was started by an incision. The bleeding time was recorded and categorized as ‘bleeding stopped at the second minute’, ‘bleeding stopped at the fourth minute’, and ‘unsuccessful’ if bleeding continued after the fourth minute. Results: In the control group, 60% of the bleeding did not stop. In the first 4 min in the Ankaferd group, the bleeding stopped in all rats; only in 1 of the rats in the chitosan group did the bleeding not stop. In stopping the bleeding in the first 4 min, Ankaferd was similar to chitosan but better than the control group; the chitosan group was similar to the control, but the p-value was close to significance. Conclusion: For major arterial bleeding, the main treatment is surgical bleeding control, but outside of the hospital we can use buffers containing Ankaferd and chitosan on the bleeding region. The results of this study should be supported with larger studies. Furthermore, in our study, healthy rats were used. New studies are needed to evaluate the results of hypovolemic and hypotensive cases with major artery bleeding. PMID:25913214

  2. Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats

    PubMed Central

    Jickling, Glen C; Ander, Bradley P; Hull, Heather; Zhan, Xinhua; Cox, Christopher; Shroff, Natasha; Dykstra-Aiello, Cheryl; Stamova, Boryana; Sharp, Frank R

    2015-01-01

    Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes. PMID:26661204

  3. Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats

    PubMed Central

    Padilla, Jaume; Jenkins, Nathan T.; Thorne, Pamela K.; Martin, Jeffrey S.; Rector, R. Scott; Akter, Sadia; Davis, J. Wade

    2015-01-01

    We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the diaphragm of OLETF rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). Our hypothesis was that exercise training would have similar effects on gene expression in the diaphragm and soleus muscle arterioles because diaphragm blood flow increases during exercise to a similar extent as in soleus. Results reveal that several canonical pathways that were significantly altered by exercise in limb skeletal muscles were not among the pathways significantly changed in the diaphragm arterioles including actin cytoskeleton signaling, role of NFAT in regulation of immune response, protein kinase A signaling, and protein ubiquitination pathway. EX training altered the expression of a smaller number of genes than did SPRINT in the DFA but induced a larger number of genes with altered expression in the D2a than did SPRINT. In fact, FDR differential expression analysis (FDR, 10%) indicated that only two genes exhibited altered expression in D2a of SPRINT rats. Very few of the genes that exhibited altered expression in the DFA or D2a were also altered in limb muscle arterioles. Finally, results indicate that the 2a arterioles of soleus muscle (S2a) from endurance-trained animals and the DFA of SPRINT animals exhibited the largest number of genes with altered expression. PMID:26183478

  4. Low-speed treadmill running exercise improves memory function after transient middle cerebral artery occlusion in rats.

    PubMed

    Shimada, Haruka; Hamakawa, Michiru; Ishida, Akimasa; Tamakoshi, Keigo; Nakashima, Hiroki; Ishida, Kazuto

    2013-04-15

    Physical exercise may enhance the recovery of impaired memory function in stroke rats. However the appropriate conditions of exercise and the mechanisms underlying these beneficial effects are not yet known. Therefore, the purpose of this study was to investigate the effect exercise intensity on memory function after cerebral infarction in rats. The animals were subjected to middle cerebral artery occlusion (MCAO) for 90 min to induce stroke and were randomly assigned to four groups; Low-Ex, High-Ex, Non-Ex and Sham. On the fourth day after surgery, rats in the Low-Ex and High-Ex groups were forced to exercise using a treadmill for 30 min every day for four weeks. Memory functions were examined during the last 5 days of the experiment (27-32 days after MCAO) by three types of tests: an object recognition test, an object location test and a passive avoidance test. After the final memory test, the infarct volume, number of neurons and microtubule-associated protein 2 (MAP2) immunoreactivity in the hippocampus were analyzed by histochemistry. Memory functions in the Low-Ex group were improved in all tests. In the High-Ex group, only the passive avoidance test improved, but not the object recognition or object location tests. Both the Low-Ex and High-Ex groups had reduced infarct volumes. Although the number of neurons in the hippocampal dentate gyrus of the Low-Ex and High-Ex groups was increased, the number for the Low-Ex group increased more than that for the High-Ex group. Moreover hippocampal MAP2 immunoreactivity in the High-Ex group was reduced compared to that in the Low-Ex group. These data suggest that the effects of exercise on memory impairment after cerebral infarction depend on exercise intensity.

  5. Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2 S-synthesizing pathways.

    PubMed

    Prieto-Lloret, Jesus; Shaifta, Yasin; Ward, Jeremy P T; Aaronson, Philip I

    2015-01-15

    An increase in the H2 S (hydrogen sulphide, hereafter sulphide) concentration in pulmonary artery smooth muscle cells (PASMCs) has been proposed to mediate hypoxic pulmonary vasoconstriction (HPV). We evaluated this hypothesis in isolated rat intrapulmonary arteries (IPAs) by examining the effects of the sulphide precursor cysteine and sulphide-synthesis blockers on HPV and also on normoxic pulmonary vasoconstriction (NPV) stimulated by prostaglandin F2α (PGF2α ) and by the drug LY83583, which causes contraction in IPAs by increasing cellular reactive oxygen species levels. Experiments with several blockers of cystathionine γ-lyase (CSE), the enzyme responsible for sulphide synthesis in the vasculature, demonstrated that propargylglycine (PAG, 1 mm) had little or no effect on the NPV caused by PGF2α or LY83583. Conversely, other CSE antagonists tested, aminooxyacetic acid (AOAA, 100 μm), β-cyanoalanine (BCA, 500 μm) and hydroxylamine (HA, 100 μm), altered the NPV to PGF2α (BCA increased, HA inhibited) and/or LY83583 (BCA increased, AOAA and HA inhibited). Preincubating IPAs in physiological saline solution (PSS) containing 1 mm cysteine increased the amplitude of the NPV to PGF2(α) by ∼50%, and had a similar effect on HPV elicited by hypoxic challenge with 0% O2 . The enhancement of both responses by cysteine was abolished by pretreatment with 1 mm PAG. Measurements carried out with an amperometric electrode demonstrated that incubation with 1 mm cysteine under anoxic conditions (to minimize sulphide oxidation) greatly potentiated the release of sulphide from pieces of rat liver and that this release was strongly antagonized by PAG, indicating that at this concentration PAG could enter cells intact and antagonize CSE. PAG at 1 mm had no effect on HPV recorded in control PSS, or in PSS supplemented with physiological concentrations of cysteine (10 μm), cystine (50 μm) and glutamate (100 μm) in order to prevent the possible depletion of intracellular

  6. Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2 S-synthesizing pathways.

    PubMed

    Prieto-Lloret, Jesus; Shaifta, Yasin; Ward, Jeremy P T; Aaronson, Philip I

    2015-01-15

    An increase in the H2 S (hydrogen sulphide, hereafter sulphide) concentration in pulmonary artery smooth muscle cells (PASMCs) has been proposed to mediate hypoxic pulmonary vasoconstriction (HPV). We evaluated this hypothesis in isolated rat intrapulmonary arteries (IPAs) by examining the effects of the sulphide precursor cysteine and sulphide-synthesis blockers on HPV and also on normoxic pulmonary vasoconstriction (NPV) stimulated by prostaglandin F2α (PGF2α ) and by the drug LY83583, which causes contraction in IPAs by increasing cellular reactive oxygen species levels. Experiments with several blockers of cystathionine γ-lyase (CSE), the enzyme responsible for sulphide synthesis in the vasculature, demonstrated that propargylglycine (PAG, 1 mm) had little or no effect on the NPV caused by PGF2α or LY83583. Conversely, other CSE antagonists tested, aminooxyacetic acid (AOAA, 100 μm), β-cyanoalanine (BCA, 500 μm) and hydroxylamine (HA, 100 μm), altered the NPV to PGF2α (BCA increased, HA inhibited) and/or LY83583 (BCA increased, AOAA and HA inhibited). Preincubating IPAs in physiological saline solution (PSS) containing 1 mm cysteine increased the amplitude of the NPV to PGF2(α) by ∼50%, and had a similar effect on HPV elicited by hypoxic challenge with 0% O2 . The enhancement of both responses by cysteine was abolished by pretreatment with 1 mm PAG. Measurements carried out with an amperometric electrode demonstrated that incubation with 1 mm cysteine under anoxic conditions (to minimize sulphide oxidation) greatly potentiated the release of sulphide from pieces of rat liver and that this release was strongly antagonized by PAG, indicating that at this concentration PAG could enter cells intact and antagonize CSE. PAG at 1 mm had no effect on HPV recorded in control PSS, or in PSS supplemented with physiological concentrations of cysteine (10 μm), cystine (50 μm) and glutamate (100 μm) in order to prevent the possible depletion of intracellular

  7. Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

    PubMed

    Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

    2013-11-30

    l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension.

  8. Agmatine Induced NO Dependent Rat Mesenteric Artery Relaxation and its Impairment in Salt-Sensitive Hypertension

    PubMed Central

    Gadkari, Tushar V.; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M.; Joshi, Mahesh S.

    2013-01-01

    L-arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. L-arginine initiated relaxations (EC50, 5.8 ± 0.7 mM; n = 9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3 ± 1.3 mM; n = 5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7 ± 12.1 μM; n = 22), which was compromised by L-NAME (L-NG-Nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9 ± 23.4 μM; n = 5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. PMID:23994446

  9. Mulberry leaf extract restores arterial pressure in streptozotocin-induced chronic diabetic rats.

    PubMed

    Naowaboot, Jarinyaporn; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol; Kukongviriyapan, Upa; Nakmareong, Saowanee; Itharat, Arunporn

    2009-08-01

    Free radical-induced vascular dysfunction plays a key role in the pathogenesis of vascular disease found in chronic diabetic patients. Morus alba (MA) leaf extract is promoted for good health especially in diabetic patients. Interestingly, antidiabetic and antioxidant activities of MA have been reported in experimental animals. Thus, the hypothesis of this study was that the long-term treatment with MA could improve vascular reactivity of chronic diabetic rats. To test this hypothesis, we examined the effect of long-term treatment with MA on the vascular responses to vasoactive agents in streptozotocin-induced chronic diabetic rats. The diabetic rats were either orally administered with distilled water, MA (0.25, 0.5 and 1 g/kg per day) or subcutaneously injected with insulin (4 U/kg per day) for 8 weeks. After each treatment, the fasting blood glucose, blood pressure, vascular responses to vasoactive agents and tissue malondialdehyde were examined. Morus alba at the doses of 0.5 and 1 g/kg, which significantly reduced blood glucose level, also significantly decreased the high blood pressure in diabetic rats. Vascular responses of the chronic diabetic rats to vasodilators, acetylcholine (3-30 nmol/kg) and sodium nitroprusside (1-10 nmol/kg) were significantly suppressed by 26% to 44% and 45% to 77% respectively, whereas those to vasoconstrictor, phenylephrine (0.01-0.1 micromol/kg) were significantly increased by 23% to 38% as compared to normal rats. Interestingly, the administration of 0.5 and 1 g/kg MA or 4 U/kg insulin significantly restored the vascular reactivities of diabetic rats. Moreover, 8 weeks of diabetes resulted in the elevation of malondialdehyde content in tissues (liver, kidney, heart, and aorta), and MA treatment significantly lessened this increase. These results provide the first evidence for the efficacy of MA in restoring the vascular reactivity of diabetic rats, the mechanism of which may associate with the alleviation of oxidative stress

  10. Evaluation of the middle cerebral artery occlusion techniques in the rat by in-vitro 3-dimensional micro- and nano computed tomography

    PubMed Central

    2010-01-01

    Background Animal models of focal cerebral ischemia are widely used in stroke research. The purpose of our study was to evaluate and compare the cerebral macro- and microvascular architecture of rats in two different models of permanent middle cerebral artery occlusion using an innovative quantitative micro- and nano-CT imaging technique. Methods 4h of middle cerebral artery occlusion was performed in rats using the macrosphere method or the suture technique. After contrast perfusion, brains were isolated and scanned en-bloc using micro-CT (8 μm)3 or nano-CT at 500 nm3 voxel size to generate 3D images of the cerebral vasculature. The arterial vascular volume fraction and gray scale attenuation was determined and the significance of differences in measurements was tested with analysis of variance [ANOVA]. Results Micro-CT provided quantitative information on vascular morphology. Micro- and nano-CT proved to visualize and differentiate vascular occlusion territories performed in both models of cerebral ischemia. The suture technique leads to a remarkable decrease in the intravascular volume fraction of the middle cerebral artery perfusion territory. Blocking the medial cerebral artery with macrospheres, the vascular volume fraction of the involved hemisphere decreased significantly (p < 0.001), independently of the number of macrospheres, and was comparable to the suture method. We established gray scale measurements by which focal cerebral ischemia could be radiographically categorized (p < 0.001). Nano-CT imaging demonstrates collateral perfusion related to different occluded vessel territories after macrosphere perfusion. Conclusion Micro- and Nano-CT imaging is feasible for analysis and differentiation of different models of focal cerebral ischemia in rats. PMID:20509884

  11. Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: involvement with NO-sGC-cGKs pathway.

    PubMed

    Ma, Lu; Wang, Ke; Shang, Jianyu; Cao, Chengzhang; Zhen, Panpan; Liu, Xin; Wang, Wen; Zhang, Hui; Du, Yunhui; Liu, Huirong

    2014-01-01

    Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO-) in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3-4 months olds) and aging (20 months olds) male SD rats were randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0% ± 4.5% vs. 50.4% ± 2.9%, P<0.01). And the endothelium-independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3 ± 1.0 nmol/ml vs. 3.3 ± 1.4 nmol/ml, P<0.05) and increased NT expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO- or its sources (P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05). The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction.

  12. Secondhand tobacco smoke, arterial stiffness, and altered circadian blood pressure patterns are associated with lung inflammation and oxidative stress in rats.

    PubMed

    Gentner, Nicole J; Weber, Lynn P

    2012-02-01

    Chronic smoking and secondhand tobacco smoke exposure are major risk factors for cardiovascular disease that are known to adversely alter the structural and mechanical properties of arteries. The objective of this study was to determine the effects of subchronic secondhand tobacco smoke exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in conscious, unsedated radiotelemetry-implanted rats. Pulse wave change in pressure over time (dP/dt) was used an indicator of arterial stiffness and was compared with both structural (wall thickness) and functional (nitric oxide production and bioactivity and endothelin-1 levels) features of the arterial wall. In addition, histology of lung, heart, and liver was examined as well as pulmonary and hepatic detoxifying enzyme activity (cytochrome P450, specifically CYP1A1). Subchronic secondhand tobacco smoke exposure altered the circadian pattern of heart rate and blood pressure, with a loss in the normal dipping pattern of blood pressure during sleep. Secondhand tobacco smoke exposure also increased pulse wave dP/dt in the absence of any structural modifications in the arterial wall. Furthermore, although nitric oxide production and endothelin-1 levels were not altered by secondhand tobacco smoke, there was increased inactivation of nitric oxide as indicated by peroxynitrite production. Increased lung neutrophils or pulmonary CYP1A1 may be responsible for the increase in oxidative stress in rats exposed to secondhand tobacco smoke. In turn, this may be related to the observed failure of blood pressure to dip during periods of sleep and a possible increase in arterial stiffness.

  13. Secondhand tobacco smoke, arterial stiffness, and altered circadian blood pressure patterns are associated with lung inflammation and oxidative stress in rats.

    PubMed

    Gentner, Nicole J; Weber, Lynn P

    2012-02-01

    Chronic smoking and secondhand tobacco smoke exposure are major risk factors for cardiovascular disease that are known to adversely alter the structural and mechanical properties of arteries. The objective of this study was to determine the effects of subchronic secondhand tobacco smoke exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in conscious, unsedated radiotelemetry-implanted rats. Pulse wave change in pressure over time (dP/dt) was used an indicator of arterial stiffness and was compared with both structural (wall thickness) and functional (nitric oxide production and bioactivity and endothelin-1 levels) features of the arterial wall. In addition, histology of lung, heart, and liver was examined as well as pulmonary and hepatic detoxifying enzyme activity (cytochrome P450, specifically CYP1A1). Subchronic secondhand tobacco smoke exposure altered the circadian pattern of heart rate and blood pressure, with a loss in the normal dipping pattern of blood pressure during sleep. Secondhand tobacco smoke exposure also increased pulse wave dP/dt in the absence of any structural modifications in the arterial wall. Furthermore, although nitric oxide production and endothelin-1 levels were not altered by secondhand tobacco smoke, there was increased inactivation of nitric oxide as indicated by peroxynitrite production. Increased lung neutrophils or pulmonary CYP1A1 may be responsible for the increase in oxidative stress in rats exposed to secondhand tobacco smoke. In turn, this may be related to the observed failure of blood pressure to dip during periods of sleep and a possible increase in arterial stiffness. PMID:22140051

  14. Endothelin-1 contributes to endothelial dysfunction and enhanced vasoconstriction through augmented superoxide production in penile arteries from insulin-resistant obese rats: role of ETA and ETB receptors

    PubMed Central

    Sánchez, A; Martínez, P; Muñoz, M; Benedito, S; García-Sacristán, A; Hernández, M; Prieto, D

    2014-01-01

    Background and Purpose We assessed whether endothelin-1 (ET-1) inhibits NO and contributes to endothelial dysfunction in penile arteries in a model of insulin resistance-associated erectile dysfunction (ED). Experimental Approach Vascular function was assessed in penile arteries, from obese (OZR) and lean (LZR) Zucker rats, mounted in microvascular myographs. Changes in basal and stimulated levels of superoxide (O2−) were detected by lucigenin-enhanced chemiluminescence and ET receptor expression was determined by immunohistochemistry. Key Results ET-1 stimulated acute O2− production that was blunted by tempol and the NADPH oxidase inhibitor, apocynin, but markedly enhanced in obese animals. ET-1 inhibited the vasorelaxant effects of ACh and of the NO donor S-nitroso-N-acetyl-DL-penicillamine in arteries from both LZR and OZR. Selective ETA (BQ123) or ETB receptor (BQ788) antagonists reduced both basal and ET-1-stimulated superoxide generation and reversed ET-1-induced inhibition of NO-mediated relaxations in OZR, while only BQ-123 antagonized ET-1 actions in LZR. ET-1-induced vasoconstriction was markedly enhanced by NO synthase blockade and reduced by endothelium removal and apocynin. In endothelium-denuded penile arteries, apocynin blunted augmented ET-1-induced contractions in OZR. Both ETA and ETB receptors were expressed in smooth muscle and the endothelial layer and up-regulated in arteries from OZR. Conclusions and Implications ET-1 stimulates ETA-mediated NADPH oxidase-dependent ROS generation, which inhibits endothelial NO bioavailability and contributes to ET-1-induced contraction in healthy penile arteries. Enhanced vascular expression of ETB receptors contributes to augmented ROS production, endothelial dysfunction and increased vasoconstriction in erectile tissue from insulin-resistant obese rats. Hence, antagonism of ETB receptors might improve the ED associated with insulin-resistant states. PMID:25091502

  15. Epidermal growth factor-like repeats of tenascin-C-induced constriction of cerebral arteries via activation of epidermal growth factor receptors in rats.

    PubMed

    Fujimoto, Masashi; Shiba, Masato; Kawakita, Fumihiro; Liu, Lei; Nakasaki, Asuka; Shimojo, Naoshi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-07-01

    Tenascin-C (TNC), one of matricellular proteins, has been suggested to be involved in cerebral vasospasm after aneurysmal subarachnoid hemorrhage. However, the mechanisms of how TNC constricts cerebral arteries remain unclear. The aim of this study was to examine if epidermal growth factor (EGF)-like repeats of TNC is involved in TNC-induced constriction of cerebral arteries in rats via EGF receptor (EGFR) activation. Two dosages of recombinant TNC (r-TNC) consisting of the EGF-like repeats was administered intracisternally to healthy rats, and its vasoconstrictor effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72 hours after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24 hours. The effects of a selective EGFR tyrosine kinase inhibitor (AG1478) on r-TNC-induced vasoconstriction were evaluated by neurobehavioral tests, India-ink angiography and immunohistochemistry at 24 hours after the administration. A higher dosage of r-TNC induced cerebral arterial constriction more severely, which continued for 48 hours. The effects were associated with the activation of EGFR and extracellular signal-regulated kinase (ERK)1/2 in the smooth muscle cell layer of the constricted cerebral artery, while c-Jun N-terminal kinase and p38 were not activated. AG1478 blocked r-TNC-induced vasoconstrictive effects, as well as activation of EGFR and ERK1/2. These findings demonstrate that TNC induces constriction of cerebral arteries via activation of EGFR and ERK1/2.

  16. Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by (14C)iodoantipyrine autoradiography following middle cerebral artery occlusion

    SciTech Connect

    Tamura, A.; Graham, D.I.; McCulloch, J.; Teasdale, G.M.

    1981-01-01

    Local cerebral blood flow has been measured by quantitative autoradiography, employing (14C)iodoantipyrine as tracer, in rats killed half an hour after occlusion of the middle cerebral artery. The results were compared with pattern of local cerebral blood flow (CBF) in sham-operated rats and with neuropathological findings. In every animal there was a profound reduction (to 13% of control levels)in blood flow in the neocortex previously by the occluded artery. The level of blood flow in the areas in which ischaemic brain damage occurred was 0.24 +/- 0.03 ml g-1 min-1 (mean +/- SEM). this level of CBF is considerably greater than that reported following a similar surgical procedure in cats and primates. Moderate reductions in blood flow were also seen outside the territory of the occluded artery and in parts of the opposite hemisphere. Absolute increases in blood flow (hyperaemia) were seen only in the substantia nigra and globus pallidus ipsilateral to the occlusion. It is of the middle cerebral artery are reflections of alterations in neuronal function and metabolic activity secondary to the ischaemic lesion.

  17. Effects of quercetin on intracavernous pressure and expression of nitrogen synthase isoforms in arterial erectile dysfunction rat model

    PubMed Central

    Zhang, Yueyang; Huang, Changting; Liu, Shaoming; Bai, Jianqi; Fan, Xiaojing; Guo, Jun; Jia, Yingyu; Zhang, Zhijie; Chen, Xiaojun; Jia, Yusen; Zhang, Ping; Wang, Bin; Zhang, Xiuju

    2015-01-01

    Object: Oxidative stress involved in the regulation of arterial erectile dysfunction (A-ED). Previously report have indicated that quercetin have an antioxidant effect. In the current study, we have established the rats’ model for study the therapeutic effect of quercetin on A-ED and further investigated the molecular mechanism of action. Methods: Wistar rats were divided into sham group, A-ED group, A-ED group with low dose of quercetin, and A-ED group with high dose of quercetin. Intracavernous pressure (ICP) and mean arterial pressure (MBp) are two important indicators used for evaluation the A-ED. The changes of ICP and MBp were determined by cavernous nerve electrostimulation after treatment of quercetin at indicated doses. The expression of nitric oxide synthase (NOS) subtypes was detected by RT-PCR and Western blotting. Results: Our results indicated that ICP was significantly reduced in A-ED rats model compared with sham group, and was significantly increased after quercetin treatment (P < 0.01), while no significant effect on the MBp. The data also showed that sGC inhibitor ODQ and NOS inhibitor LNNA can significantly inhibited the ICP which induced by quercetin. These results suggest that NO-cGMP signaling pathway plays a crucial role in A-ED. Then, we found that the mRNA and protein levels of eNOS were significantly reduced in A-ED group compared with sham group. After treated with quercetin may cause the eNOS RNA and protein were significantly up-regulated (P < 0.01), showing a dose-dependent effect. iNOS expression have a certain degree of increased after quercetin treatment. nNOS expression was not significantly increased before and after treated with quercetin. In a word, quercetin can improved the A-ED by up-regulated ICP, which related to up-regulation of NO-cGMP signaling pathway. Conclusion: Preliminary results of this study suggested that quercetin protected expression and function of eNOS in cavernous endothelial cells, and restored part of

  18. Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries

    PubMed Central

    Wu, Xiaochun; Richards, Nicholas T; Johns, Edward J; Kohsaka, Takeo; Nakamura, Akio; Okada, Hidechika

    1997-01-01

    This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120–200 μm in diameter, incubated with a selective agonist and the novel ‘antisense' peptide to part of the human endothelinA receptor. Groups of vessels (n=6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC50 of 8.16±0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum). Preincubation of six vessels with the antisense peptide ETR p1/f1 at 1 μM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 μM ETR p1/f1, there was a significant shift of the concentration-response curve and a lower pEC50 at 7.78±0.09 M (P<0.05). At the highest concentrations of ETR p1/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 μM, only reached some 10% of the maximal achievable contraction. Increasing ET-1 concentrations up to 2 μM in vessels incubated with 40 μM ETR-p1/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P<0.001) by approximately one log unit with a pEC50 of 7.13±0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors. At the highest concentrations tested, 40 μM, ETR-p1/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions. Together, these data suggest that at the rat renal arcuate artery the endothelinA receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel

  19. Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites.

    PubMed

    Kurahashi, K; Shirahase, H; Nakamura, S; Tarumi, T; Koshino, Y; Wang, A M; Nishihashi, T; Shimizu, Y

    2001-10-01

    Nicotine caused a contraction of the rat coronary artery in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME) and arachidonic acid, and did not in the absence of these agents. The present experiments were undertaken to pharmacologically characterize the nicotine-induced contraction in ring preparations of the rat coronary artery. The contraction was abolished by chemical removal of endothelium saponin. Oxygen radical scavengers, superoxide dismutase and catalase, significantly attenuated the contraction. Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimesulide and NS-389) slightly attenuated the contraction. A TXA2 synthetase inhibitor (OKY-046) attenuated the contraction to a small extent only at high concentrations. A TXA2 receptor antagonist (S-1452) attenuated the contraction in a concentration-dependent manner. A nicotinic receptor antagonist (hexamethonium) attenuated the contraction in part and an alpha-adrenoceptor antagonist (prazosin) nearly abolished the contraction. From these results, it was suggested that the contraction induced by nicotine in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent, and involves reactive oxygen species and endothelial COX-1 metabolites of arachidonic acid. Part of the contraction is probably due to release of norepinephrine. PMID:11811354

  20. Adventitial Alterations Are the Main Features in Pulmonary Artery Remodeling due to Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats

    PubMed Central

    Brito, Julio; Siques, Patricia; Arribas, Silvia M.; López de Pablo, Angel L.; González, M. Carmen; Naveas, Nelson; Flores, Karen; León-Velarde, Fabiola; Pulido, Ruth; Ordenes, Stefany; López, M. Rosario

    2015-01-01

    Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer. PMID:25738150

  1. Adventitial alterations are the main features in pulmonary artery remodeling due to long-term chronic intermittent hypobaric hypoxia in rats.

    PubMed

    Brito, Julio; Siques, Patricia; Arribas, Silvia M; López de Pablo, Angel L; González, M Carmen; Naveas, Nelson; Arriaza, Karem; Flores, Karen; León-Velarde, Fabiola; Pulido, Ruth; Ordenes, Stefany; López, M Rosario

    2015-01-01

    Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.

  2. Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

    PubMed

    Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

    2014-01-01

    Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

  3. L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure.

    PubMed

    Takemoto, Yumi

    2014-12-01

    The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors. The present study investigated cardiovascular responses to L-cysteine and L-ap4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of L-cysteine and L-AP4 in the C