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Sample records for endothelium-dependent relaxation responses

  1. Endothelium-dependent relaxation of blood vessels

    SciTech Connect

    Hynes, M.R.

    1987-01-01

    Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M/sub 2/ subtype. Inhibition of (/sup 3/H)(-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. The influence of endothelium on contractile responses was examined using the perfused caudal artery.

  2. Endothelium dependent hyperpolarization-type relaxation compensates for attenuated nitric oxide-mediated responses in subcutaneous arteries of diabetic patients.

    PubMed

    Mokhtar, Siti Safiah; Vanhoutte, Paul M; Leung, Susan Wai Sum; Yusof, Mohd Imran; Wan Sulaiman, Wan Azman; Mat Saad, Arman Zaharil; Suppian, Rapeah; Rasool, Aida Hanum Ghulam

    2016-02-29

    Diabetes impairs endothelium-dependent relaxations. The present study evaluated the contribution of different endothelium-dependent relaxing mechanisms to the regulation of vascular tone in subcutaneous blood vessels of humans with Type 2 diabetes mellitus. Subcutaneous arteries were isolated from tissues of healthy controls and diabetics. Vascular function was determined using wire myography. Expressions of proteins were measured by Western blotting and immunostaining. Endothelium-dependent relaxations to acetylcholine were impaired in arteries from diabetics compared to controls (P = 0.009). Acetylcholine-induced nitric oxide (NO)-mediated relaxations [in the presence of an inhibitor of cyclooxygenases (COX; indomethacin) and small and intermediate conductance calcium-activated potassium channel blockers (UCL1684 and TRAM 34, respectively)] were attenuated in arteries from diabetics compared to controls (P < 0.001). However, endothelium-dependent hyperpolarization (EDH)-type relaxations [in the presence of indomethacin and the NO synthase blocker, l-NAME] were augmented in arteries from diabetics compared to controls (P = 0.003). Endothelium-independent relaxations to sodium nitroprusside (NO donor) and salbutamol (β-adrenoceptor agonist) were preserved, but those to prostacyclin were attenuated in diabetics compared to controls (P = 0.017). In arteries of diabetics, protein expressions of endothelial NO synthase, prostacyclin synthase and prostacyclin receptors were decreased, but those of COX-2 were increased. These findings suggest that in human diabetes, the impairment of endothelium-dependent relaxations is caused by a diminished NO bioavailability; however, EDH appears to compensate, at least in part, for this dysfunction. PMID:26768833

  3. Marginal copper deficiency impairs endothelium-dependent relaxation responses across two generations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The generational effects of marginal copper (Cu) deficiency on vascular function have not been characterized.In this study, the vascular consequences of marginal Cu deficiency were determined by relaxation responses in mesenteric arteries of dams and two generations of offspring. Pups from dams (fir...

  4. Ultrasonic Measurement of Change in Elasticity due to Endothelium Dependent Relaxation Response by Accurate Detection of Artery-Wall Boundary

    NASA Astrophysics Data System (ADS)

    Kaneko, Takuya; Hasegawa, Hideyuki; Kanai, Hiroshi

    2007-07-01

    Ross hypothesized that an endothelial dysfunction is considered to be an initial step in atherosclerosis. Endothelial cells, which release nitric oxide (NO) in response to shear stress from blood flow, have a function of relaxing smooth muscle in the media of the arterial wall. For the assessment of the endothelial function, there is a conventional method in which the change in the diameter of the brachial artery caused by flow-mediated dilation (FMD) is measured with ultrasound. However, despite the fact that the collagen-rich hard adventitia does not respond to NO, the conventional method measures the change in diameter depending on the mechanical property of the entire wall including the adventitia. Therefore, we developed a method of measuring the change in the thickness and the elasticity of the brachial artery during a cardiac cycle using the phased tracking method for the evaluation of the mechanical property of only the intima-media region. In this study, the initial positions of echoes from the lumen-intima and media-adventitia boundaries are determined using complex template matching to accurately estimate the minute change in the thickness and the elasticity of the brachial and radial arteries. The ambiguity in the determination of such boundaries was eliminated using complex template matching, and the change in elasticity measured by the proposed method was larger than the change in inner diameter obtained by the conventional method.

  5. Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta

    PubMed Central

    Bauer, Viktor; Sotníková, Ružena; Drábiková, Katarína

    2011-01-01

    Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by α1-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A23187-induced relaxations but also the catalase sensitive hydrogen peroxide (H2O2) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O2 •–) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe2SO4/H2O2-produced hydroxyl radical (•OH) and H2O2. Thus O2 •– produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did •OH and H2O2. In the large (conduit) artery, the effects of activated neutrophils and various ROS (O2 •–, •OH and H2O2) seem to be more dependent on muscle tension than on endothelial mechanisms. PMID:22319253

  6. Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse

    SciTech Connect

    Rosenblum, W.I.; Nelson, G.H.; Povlishock, J.T.

    1987-02-01

    This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.

  7. Inhibition by quinine of endothelium-dependent relaxation of rabbit aortic strips.

    PubMed

    Gebremedhin, D; Hadházy, P; Magyar, K

    1987-12-01

    1 The effects of quinine sulphate, tetramethylammonium chloride (TMA) and tetraethylammonium chloride (TEA) (all blockers of the Ca2+-activated K+ channels) on the relaxations induced by acetylcholine (ACh), calcium ionophore A23187 and sodium nitrite were studied in helical strips of rabbit aorta. 2 The strips were contracted to a moderate stable tone with phenylephrine (10(-7) M). ACh (4 X 10(-9) to 10(-6) M) as well as A23187 (10(-8) to 3 X 10(-7) M) reduced this tone in a concentration- and endothelium-dependent manner. 3 Pretreatment of the tissues with quinine (2.5 X 10(-5) to 10(-4) M) for 60 min produced a concentration-dependent inhibition of the relaxation induced by ACh. Also 90 min incubation of the strips with TMA (3 X 10(-3) to 6.5 X 10(-2) M) or TEA (10(-3) to 3 X 10(-2) M) inhibited the ACh-evoked relaxation in a manner similar to quinine. 4 Quinine (10(-4) M, 60 min), TMA (6.5 X 10(-2) M, 90 min) or TEA (3 X 10(-2) M, 90 min) produced 5 to 10 fold reductions in the relaxant EC50 values of A23187 and ACh and depressed (by 40 to 95%) the maximal relaxations to the ionophore and ACh. 5. On a molar basis, quinine was more effective than the two tetraalkylammonium ions in reducing the endothelium-dependent relaxations of the aortic strips induced by ACh or A23187. The inhibitory actions were reversible after 60 to 90 min washout. 6. Exposure of the strips to either quinine (10-4M, 60 min), TMA (6.5 x 10-2 M, 90 min) or TEA (3 X 10-2 M, 90 min), however, did not influence significantly the relaxations evoked by sodium nitrite, a direct smooth muscle relaxant. 7. These results suggest that stimulation of the Ca2+-activated K' channels could be, at least partially, responsible for the endothelium-dependent relaxations induced by ACh or A23 187. Their activation might not be required for the endothelium-independent relaxant effects of sodium nitrite. PMID:2827827

  8. Multiple pathways underlying endothelium-dependent relaxation in the rabbit isolated femoral artery.

    PubMed Central

    Plane, F.; Pearson, T.; Garland, C. J.

    1995-01-01

    1. In isolated segments of the rabbit femoral artery stimulated with noradrenaline, both acetylcholine (1 nM-10 microM) and the calcium ionophore A23187 (1 nM-100 microM) evoked endothelium-dependent smooth muscle relaxation and hyperpolarization while bradykinin (0.01-100 nM) had no effect. 2. The nitric oxide synthase inhibitors, NG-nitro-L-arginine (L-NOARG; 100 microM; 20 min) or NG-nitro-L-arginine methyl ester (L-NAME; 100 microM; 20 min) each abolished the hyperpolarization and the majority of the relaxation to acetylcholine (maximal response reduced from 96.8 +/- 2.3% to 2.0 +/- 1.4%). 3. The potassium channel blocker, glibenclamide (10 microM; 10 min) also abolished the change in membrane potential to acetylcholine but did not modify the smooth muscle relaxation. 4. In contrast, neither L-NAME nor glibenclamide modified the comparable responses of the femoral artery to A23187, which were also unaffected by the cyclo-oxygenase inhibitor, indomethacin (10 microM). 5. In artery segments stimulated with potassium chloride (25 mM), the maximal change in tension and membrane potential evoked by A23187 (100 microM) was significantly reduced from 95.0 +/- 4.5% and 23.0 +/- 2.0 mV to 69.0 +/- 10.1% and 12.0 +/- 1.5 mV, respectively. Under these conditions L-NAME further reduced the relaxation but not the accompanying hyperpolarization to A23187. 6. Endothelium-denuded arterial segments sandwiched with endothelium-intact 'donor' segments gave qualitatively similar relaxant responses to those described above for acetylcholine and A23187.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7647981

  9. Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

    SciTech Connect

    Cheng Wei; Oike, Masahiro . E-mail: moike@pharmaco.med.kyushu-u.ac.jp; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

    2005-09-15

    The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca{sup 2+} transients and cellular uptake of L-[{sup 3}H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[{sup 3}H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine.

  10. A differential impact of lithium on endothelium-dependent but not on endothelium-independent vessel relaxation.

    PubMed

    Bosche, Bert; Molcanyi, Marek; Noll, Thomas; Rej, Soham; Zatschler, Birgit; Doeppner, Thorsten R; Hescheler, Jürgen; Müller, Daniel J; Macdonald, R Loch; Härtel, Frauke V

    2016-06-01

    Lithium is drug for bipolar disorders with a narrow therapeutic window. Lithium was recently reported to prevent stroke and protect vascular endothelium but tends to accumulate particularly in the brain and kidney. Here, adverse effects are common; however mechanisms are still vaguely understood. If lithium could also negatively influence the endothelium is unclear. We hypothesize that at higher lithium levels, the effects on endothelium reverses--that lithium also impairs endothelial-dependent relaxation of blood vessels. Vessel grafts from de-nerved murine aortas and porcine middle cerebral arteries were preconditioned using media supplemented with lithium chloride or acetate (0.4-100 mmol/L). Native or following phenylephrine-induced vasoconstriction, the relaxation capacity of preconditioned vessels was assessed by isometric myography, using acetylcholine to test the endothelium-dependent or sodium nitroprusside to test the endothelium-independent vasorelaxation, respectively. At the 0.4 mmol/L lithium concentration, acetylcholine-induced endothelium-dependent vessel relaxation was slightly increased, however, diminished in a concentration-dependent manner in vessel grafts preconditioned with lithium at higher therapeutic and supratherapeutic concentrations (0.8-100 mmol/L). In contrast, endothelium-independent vasorelaxation remained unaltered in preconditioned vessel grafts at any lithium concentration tested. Lithium elicits opposing effects on endothelial functions representing a differential impact on the endothelium within the narrow therapeutic window. Lithium accumulation or overdose reduces endothelium-dependent but not endothelium-independent vasorelaxation. The differentially modified endothelium-dependent vascular response represents an additional mechanism contributing to therapeutic or adverse effects of lithium. PMID:26875501

  11. Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension.

    PubMed

    Mayhan, W G; Faraci, F M; Heistad, D D

    1987-12-01

    The goal of this study was to determine whether endothelium-dependent responses are impaired in the cerebral microcirculation of stroke-prone spontaneously hypertensive rats (SHRSP). We measured diameters of cerebral arterioles using intravital microscopy in normotensive rats (WKY) and SHRSP (6-8 mo old). Cerebral vasodilator responses to superfusion with adenosine, which is an endothelium-independent agonist, were similar in WKY and SHRSP. In contrast, cerebral vasodilator responses to superfusion with endothelium-dependent agonists were profoundly impaired in SHRSP. Acetylcholine (10(-4) M) increased pial arteriolar diameter 23 +/- 2% (means +/- SE) in WKY and did not change arteriolar diameter in SHRSP (-2 +/- 3%, P less than 0.05 vs. WKY). Serotonin (10(-5) M) increased pial arteriolar diameter 23 +/- 1% in WKY and, in contrast, reduced diameter 11 +/- 1% in SHRSP (P less than 0.05 vs. WKY). Nitroglycerin and acetylcholine produce vasodilatation by activation of guanosine 3',5'-cyclic monophosphate (cGMP). Nitroglycerin was used to determine whether impaired responses of cerebral arterioles in SHRSP were related to altered cGMP activity. We found similar dilatation of cerebral arterioles in WKY and SHRSP in response to nitroglycerin. Thus impaired endothelium-dependent dilatation in SHRSP is not related to alteration of cGMP activity. We speculate that impairment of cerebral vasodilator responses to endothelium-dependent agonists, including vasoactive substances released by platelets, may predispose SHRSP to cerebral ischemia. PMID:3122590

  12. Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway.

    PubMed

    Lau, Yeh Siang; Ling, Wei Chih; Murugan, Dharmani; Kwan, Chiu Yin; Mustafa, Mohd Rais

    2015-07-01

    Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE), also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma "antihypertensive tea" is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs). Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase), wortmannin (30 nM) and LY294002 (20 µM; PI3 (phosphatidylinositol3)-Kinase inhibitor), N(G)-nitro-L-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS)) and ODQ (1 µM; soluble guanylyl cyclase inhibitor). Total nitrite and nitrate (NOx) level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity. PMID:26133970

  13. Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium-dependent relaxations in porcine coronary arteries via the redox-sensitive activation of endothelial nitric oxide synthase.

    PubMed

    Kim, Jong Hun; Auger, Cyril; Kurita, Ikuko; Anselm, Eric; Rivoarilala, Lalainasoa Odile; Lee, Hyong Joo; Lee, Ki Won; Schini-Kerth, Valérie B

    2013-11-30

    This study examined the ability of Aronia melanocarpa (chokeberry) juice, a rich source of polyphenols, to cause NO-mediated endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine the underlying mechanism and the active polyphenols. A. melanocarpa juice caused potent endothelium-dependent relaxations in porcine coronary artery rings. Relaxations to A. melanocarpa juice were minimally affected by inhibition of the formation of vasoactive prostanoids and endothelium-derived hyperpolarizing factor-mediated responses, and markedly reduced by N(ω)-nitro-l-arginine (endothelial NO synthase (eNOS) inhibitor), membrane permeant analogs of superoxide dismutase and catalase, PP2 (Src kinase inhibitor), and wortmannin (PI3-kinase inhibitor). In cultured endothelial cells, A. melanocarpa juice increased the formation of NO as assessed by electron paramagnetic resonance spectroscopy using the spin trap iron(II)diethyldithiocarbamate, and reactive oxygen species using dihydroethidium. These responses were associated with the redox-sensitive phosphorylation of Src, Akt and eNOS. A. melanocarpa juice-derived fractions containing conjugated cyanidins and chlorogenic acids induced the phosphorylation of Akt and eNOS. The present findings indicate that A. melanocarpa juice is a potent stimulator of the endothelial formation of NO in coronary arteries; this effect involves the phosphorylation of eNOS via the redox-sensitive activation of the Src/PI3-kinase/Akt pathway mostly by conjugated cyanidins and chlorogenic acids. PMID:23973200

  14. Polyphenol-enriched extract of oil palm fronds (Elaeis guineensis) promotes vascular relaxation via endothelium-dependent mechanisms.

    PubMed

    Abeywardena, Mahinda; Runnie, Irine; Nizar, Mohd; Suhaila, Momamed; Head, Richard

    2002-01-01

    Plant-based polyphenolic compounds have been reported to possess cardiovascular health benefits. Several dietary sources, including herbs and spices, fruits and vegetables, and tea and wine, contain an array of biologically active compounds that have been shown to be effective in retarding oxidation of low-density lipoproteins (LDL) and promoting vascular relaxation. In the present study four different plant sources, both edible and non-edible, were evaluated for potential activity. Organic extracts enriched in polyphenols were prepared from palm fronds (Elaesis guineensis); lemongrass (Cymbopogon citrates); papaya shoots (Carica papaya) and green chilli (Capsicum frutescenes) and tested for their ability to prevent in vitro oxidation of LDL, and for potential vascular relaxation actions. Rings of rat thoracic aorta and isolated perfused mesenteric vascular beds were mounted in organ baths, contracted using a half-maximal dose of noradrenaline and exposed to cumulative additions of test extracts. Palm frond extract resulted in considerable relaxation (>75%) in both preparations and was found to be endothelium-dependent as removal of endothelium or inhibition of endogenous nitric oxide (NO) led to a total loss in relaxant activity. Lemongrass extract caused a greater relaxation action in the mesenteric preparation compared to aortic rings, and appears to be mediated via NO-independent and non-prostanoid mechanisms. Of the extracts tested, palm fronds also demonstrated the highest antioxidant capacity, as determined by the ferric reducing activity/potential assay, and resulted in a significant delay (P < 0.05) in the oxidation of LDL. Collectively, these preliminary findings lend further support to the potential cardiovascular actions of plant polyphenols and also identify oil palm fronds as containing constituents that promote vascular relaxation via endothelium-dependent mechanisms. PMID:12492636

  15. Vascular Protective Effect of an Ethanol Extract of Camellia japonica Fruit: Endothelium-Dependent Relaxation of Coronary Artery and Reduction of Smooth Muscle Cell Migration

    PubMed Central

    Park, Sin-Hee; Shim, Bong-Sup; Yoon, Jun-Seong; Lee, Hyun-Ho; Lee, Hye-Won; Yoo, Seok-Bong; Wi, An-Jin; Park, Whoa-Shig; Kim, Hyun-Jung; Kim, Dong-Wok; Oak, Min-Ho

    2016-01-01

    Camellia japonica is a popular garden plant in Asia and widely used as cosmetic sources and traditional medicine. However, the possibility that C. japonica affects cardiovascular system remains unclear. The aim of the present study was to evaluate vascular effects of an extract of C. japonica. Vascular reactivity was assessed in organ baths using porcine coronary arteries and inhibition of proliferation and migration were assessed using human vascular smooth muscle cells (VSMCs). All four different parts, leaf, stem, flower, and fruits, caused concentration-dependent relaxations and C. japonica fruit (CJF) extract showed the strongest vasorelaxation and its effect was endothelium dependent. Relaxations to CJF were markedly reduced by inhibitor of endothelial nitric oxide synthase (eNOS) and inhibitor of PI3-kinase, but not affected by inhibitor of cyclooxygenase and endothelium-derived hyperpolarizing factor-mediated response. CJF induced activated a time- and concentration-dependent phosphorylation of eNOS in endothelial cells. Altogether, these studies have demonstrated that CJF is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, PI3K-eNOS-NO pathway. Moreover, CJF attenuated TNF-α induced proliferation and PDGF-BB induced migration of VSMCs. The present findings indicate that CJF could be a valuable candidate of herbal medicine for cardiovascular diseases associated with endothelial dysfunction and atherosclerosis. PMID:26697138

  16. Vascular Protective Effect of an Ethanol Extract of Camellia japonica Fruit: Endothelium-Dependent Relaxation of Coronary Artery and Reduction of Smooth Muscle Cell Migration.

    PubMed

    Park, Sin-Hee; Shim, Bong-Sup; Yoon, Jun-Seong; Lee, Hyun-Ho; Lee, Hye-Won; Yoo, Seok-Bong; Wi, An-Jin; Park, Whoa-Shig; Kim, Hyun-Jung; Kim, Dong-Wok; Oak, Min-Ho

    2015-01-01

    Camellia japonica is a popular garden plant in Asia and widely used as cosmetic sources and traditional medicine. However, the possibility that C. japonica affects cardiovascular system remains unclear. The aim of the present study was to evaluate vascular effects of an extract of C. japonica. Vascular reactivity was assessed in organ baths using porcine coronary arteries and inhibition of proliferation and migration were assessed using human vascular smooth muscle cells (VSMCs). All four different parts, leaf, stem, flower, and fruits, caused concentration-dependent relaxations and C. japonica fruit (CJF) extract showed the strongest vasorelaxation and its effect was endothelium dependent. Relaxations to CJF were markedly reduced by inhibitor of endothelial nitric oxide synthase (eNOS) and inhibitor of PI3-kinase, but not affected by inhibitor of cyclooxygenase and endothelium-derived hyperpolarizing factor-mediated response. CJF induced activated a time- and concentration-dependent phosphorylation of eNOS in endothelial cells. Altogether, these studies have demonstrated that CJF is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, PI3K-eNOS-NO pathway. Moreover, CJF attenuated TNF-α induced proliferation and PDGF-BB induced migration of VSMCs. The present findings indicate that CJF could be a valuable candidate of herbal medicine for cardiovascular diseases associated with endothelial dysfunction and atherosclerosis. PMID:26697138

  17. The DPP-4 inhibitor linagliptin and the GLP-1 receptor agonist exendin-4 improve endothelium-dependent relaxation of rat mesenteric arteries in the presence of high glucose.

    PubMed

    Salheen, S M; Panchapakesan, U; Pollock, C A; Woodman, O L

    2015-04-01

    The aim of the study was to investigate the effects of the DPP-4 inhibitors and GLP-1R agonist, exendin-4 on the mechanism(s) of endothelium-dependent relaxation in rat mesenteric arteries exposed to high glucose concentration (40 mM). Organ bath techniques were employed to investigate vascular endothelial function in rat mesenteric arteries in the presence of normal (11 mM) or high (40 mM) glucose concentrations. Pharmacological tools (1μM TRAM-34, 1μM apamin, 100 nM Ibtx, 100 μM l-NNA, 10 μM ODQ) were used to distinguish between NO and EDHF-mediated relaxation. Superoxide anion levels were assessed by L-012 and lucigenin enhanced-chemiluminescence techniques. Incubation of mesenteric rings with high glucose for 2 h caused a significant increase in superoxide anion generation and a significant impairment of endothelium-dependent relaxation. Exendin-4 and DPP-4 inhibitor linagliptin, but not sitagliptin or vildagliptin, significantly reduced vascular superoxide and improved endothelium-dependent relaxation in the presence of high glucose. The beneficial actions of exendin-4, but not linagliptin, were attenuated by the GLP-1R antagonist exendin fragment (9-39). Further experiments demonstrated that the presence of high glucose impaired the contribution of both nitric oxide and endothelium-dependent hyperpolarisation to relaxation and that linagliptin improved both mechanisms involved in endothelium-dependent relaxation. These findings demonstrate that high glucose impaired endothelium-dependent relaxation can be improved by exendin-4 and linagliptin, likely due to their antioxidant activity and independently of any glucose lowering effect. PMID:25697548

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

    PubMed Central

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

    2015-01-01

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

  19. Is the presence of hyperlipidemia associated with impairment of endothelium-dependent neointimal relaxation after percutaneous transluminal coronary angioplasty?

    PubMed

    Sakai, A; Hirayama, A; Adachi, T; Nanto, S; Hori, M; Inoue, M; Kamada, T; Kodama, K

    1996-01-01

    To determine whether hyperlipidemia affects the endothelium-dependent vasomotor response along the dilated vessel after percutaneous transluminal coronary angioplasty (PTCA), we evaluated 32 patients with one-vessel disease, 3-6 months after successful PTCA without restenosis. Fourteen patients had mild stenotic lesions not subjected to PTCA (non-PTCA sites) in addition to the PTCA sites. Vessel diameter changes at 32 PTCA and 36 non-PTCA sites were assessed by quantitative angiography, before and after intracoronary injection of acetylcholine (20 micrograms to the right and 50 micrograms to the left coronary artery) and of nitroglycerin (0.1-0.3 mg). The acetylcholine response ranged from 46% (dilation) to -100% (constriction). All coronary arteries were dilated in response to nitroglycerin, which suggested preservation of the function of vascular smooth muscle, and the presence of an abnormality in endothelial function in those patients with a constrictor response to acetylcholine. There was a negative correlation between the acetylcholine response and the serum total cholesterol level at PTCA sites (r = -0.37; P = 0.038) and at non-PTCA sites (r = -0.46; P = 0.005). These findings indicate that hyperlipidemia is associated with a loss of endothelium-dependent vasodilation, not only at non-PTCA but also at PTCA sites, at which restoration of endothelial function might have occurred. They also suggest that hyperlipidemia may be related to the functional state of the regenerated endothelium at sites where PTCA had been previously performed. PMID:9129246

  20. Singlet oxygen scavengers affect laser-dye impairment of endothelium-dependent responses of brain arterioles.

    PubMed

    Rosenblum, W I; Nelson, G H

    1996-04-01

    This study investigates the possible role of singlet oxygen in accounting for the inhibitory effect of laser-dye injury on endothelium-dependent dilations. The combination of helium-neon (HeNe) laser (20-s exposure) and intravascular Evans blue impairs endothelium-dependent dilation of mouse pial arterioles by acetylcholine (ACh), bradykinin (BK), and calcium ionophore A23187. Each has a different endothelium-derived mediator (EDRFACh, EDRFBK, EDRFionophore, respectively). In this study, diameters at a craniotomy site were monitored in vivo with an image splitter-television microscope. The laser-dye injury, as usual, abolished the responses 10 and 30 min after injury, with recovery, complete or partial, at 60 min. Dilations by sodium nitroprusside, an endothelium-independent dilator, were not affected by laser-dye. When the singlet oxygen scavengers L-histidine (10(-3) M) and L-tryptophan (10(-2) M) were added to the suffusate over the site, the responses to ACh at 10 and 30 min were relatively intact, the response to BK was partly protected at 10 min only, and the response to ionophore was still totally impaired at 10 and 30 min. Lysine, a nonscavenging amino acid, had no protective effects with any dilator. We postulate that a heat-induced injury initiates a chain of events resulting in prolonged singlet oxygen generation by the endothelial cell (not by the dye). We postulate further that destruction of EDRFACh by singlet oxygen is responsible for laser-dye inhibition of ACh and that generation of the radical must continue for > or = 30 min. On the other hand, the heat injury itself is probably responsible for the elimination of the response to ionophore. Heat plus singlet oxygen generated by heat-damaged tissue may initially impair the response to BK, but by 30 min only the effects of some other factor, presumably heat injury, account for the impaired response to BK. PMID:8967364

  1. Fruit juice-induced endothelium-dependent relaxations in isolated porcine coronary arteries: evaluation of different fruit juices and purees and optimization of a red fruit juice blend.

    PubMed

    Auger, Cyril; Kim, Jong-Hun; Trinh, Sandrine; Chataigneau, Thierry; Popken, Anne M; Schini-Kerth, Valérie B

    2011-05-01

    Numerous studies have indicated that several polyphenol-rich sources such as red wine and green tea are potent inducers of endothelium-dependent relaxations in isolated arteries. As various fruits and berries are known to contain high levels of polyphenols, the aim of the present study was to assess the ability of selected pure fruit juices and purees as well as blends to cause endothelium-dependent relaxations in isolated arteries. Vascular reactivity was assessed using porcine coronary artery rings, and fruit juices, purees and blends were characterized for their content in vitamin C, total phenolic, sugar and antioxidant activity. Fruit juices and purees caused variable concentration-dependent relaxations, with blackcurrant, aronia, cranberry, blueberry, lingonberry, and grape being the most effective fruits. Several blends of red fruits caused endothelium-dependent relaxations. Relaxations to blend D involved both a NO- and an EDHF-mediated components. The present findings indicate that some berries and blends of red fruit juices are potent inducers of endothelium-dependent relaxations in the porcine coronary artery. This effect involves both endothelium-derived NO and EDHF, and appears to be dependent on their polyphenolic composition rather than on the polyphenolic content. PMID:21779562

  2. Impaired endothelium-dependent and -independent relaxation of aorta from diabetic rats.

    PubMed

    Yakubu, M A; Sofola, O A; Igbo, I; Oyekan, A O

    2012-01-01

    Vascular complication in diabetes has been reported to be due to the effects of chronic high blood glucose on the vascular system. Different relaxation mechanisms exist in the vasculature and effect of chronic high glucose on vascular relaxation mechanisms is not clearly understood. We assessed the effect of streptozotocin (STZ, 70 mg/kg, for 12 wks)-induced diabetes on vascular reactivity to isoproterenol (Isop, 10-9-10-5 M), a cAMP-dependent agent, acetylcholine (ACh, 10-9-10-5 M), a stimulant of NO (nitric oxide) synthase, sodium nitroprusside (SNP, 10-10-10-5 M), NO donor, or bradykinin (BK, 10-9-10-5 M) in the rat isolated aortic ring. Isop, ACh, SNP, or BK dose-dependently relaxed phenylephrine (PE, 10-7 M) pre-constricted ring producing a maximum relaxation of 82 % for Isop (10-5 M), 85 % for ACh (10-5 M), 100 % for SNP (10-6 M), and 30 % for BK (10-5 M) respectively. STZ attenuated Isop, ACh, and BK-induced relaxation by 45 % (n=7, pn (Fig. 5, Ref. 24). PMID:22394031

  3. Increased Superoxide Anions Level may be Related with Impaired Endothelium-Dependent Relaxation of Cerebral and Carotid Arteries in Simulated Microgravity Rats

    NASA Astrophysics Data System (ADS)

    Ma, Jin; Zhang, Ran; Ren, Xin-Ling

    2008-06-01

    Our previous works showed that there is a significant increase in nitrite and nitrate content of cerebral and carotid arteries of hindlimb unweighting rats, and this result suggests that NOS activity or NO production may be increased by HU in the cerebral and carotid arteries ,and this may result in a enhanced endothelium-dependent dilatory responses in these artery of hindlimb unweighting rats. The aim of this work is to investigate the effects of hindlimb unweighting on endothelium mediated relaxation and find the possible mechanisms which may result in the alteration. Twenty male healthy SD rats, which body weight ranged from 250g to 280g, were divided into control and hindlimb unweighting simulated microgravity groups randomly. After three weeks, the basilar artery and carotid artery were isolated and arterial dilatory responsiveness were examined in vitro using isolated arterial rings from rats. And the Superoxide Anions Levels were detected by oxidation-sensitive dye dihydroethidium and laser scanning confocal microscope. The data showed: Dilatory responses of both basilar and carotid arterial rings to Acetylcholine(10-10~10-4 mol/L ) was decreased in simulated microgravity rats as compared with that of controls, but dilatory responses of isolated arterial rings to Sodium Nitroprussid (10-10~10-4 mol/L ) was similar in both simulated Microgravity rats and control rats, and stronger superoxide anions signals were detected in basilar and carotid arteries from HU rats, while compared with that of control rats. These results indicate that endothelium-dependent relaxation of both basilar artery and carotid artery have been diminished by 3-week hindlimb unweighting, and increased superoxide anions levels may contribute to this alteration.

  4. Paullinia pinnata extracts rich in polyphenols promote vascular relaxation via endothelium-dependent mechanisms.

    PubMed

    Zamble, Alexis; Carpentier, Marie; Kandoussi, Abdelmejid; Sahpaz, Sevser; Petrault, Olivier; Ouk, Tawarak; Hennuyer, Nathalie; Fruchart, Jean-Charles; Staels, Bart; Bordet, Régis; Duriez, Patrick; Bailleul, François; Martin-Nizard, Françoise

    2006-04-01

    Paullinia pinnata L. (Sapindaceae) is an African tropical plant whose roots and leaves are used in traditional medicine for many purposes, especially for erectile dysfunction, but its action mechanism is unknown. P. pinnata root and leaf methanolic extracts are rich in phenolic compounds. This study shows that both extracts are highly antioxidative and induce a slight transcriptional activity of peroxisome proliferator activated receptor-alpha. They also increased and decreased endothelial nitric oxide synthase and endothelin-1 mRNA levels in bovine aortic endothelial cells, respectively. In this study P. pinnata methanolic extracts in cumulative doses elicited in a dose-dependent manner the relaxation of phenylephrine precontracted isolated rat aortic rings. N-nitro-L-arginine methyl ester significantly attenuated the capacity of both extracts to induce arterial relaxation, indicating that this arterial relaxation was mediated by endothelial nitric oxide release. It could be suggested that the arterial relaxation induced by both extracts could be mainly linked to their capacities to inhibit nitric oxide oxidation through their antioxidant properties. PMID:16680075

  5. Involvement of histamine in endothelium-dependent relaxation of mesenteric lymphatic vessels

    PubMed Central

    Nizamutdinova, Irina Tsoy; Maejima, Daisuke; Nagai, Takashi; Bridenbaugh, Eric; Thangaswamy, Sangeetha; Chatterjee, Victor; Meininger, Cynthia J.; Gashev, Anatoliy A.

    2014-01-01

    Objectives The knowledge of the basic principles of lymphatic function, still remains, to a large degree, rudimentary and will require significant research efforts. Recent studies of the physiology of the mesenteric lymphatic vessels (MLVs) suggested the presence of an endothelium-derived relaxing factor (EDRF) other than nitric oxide. In this study we tested the hypothesis that lymphatic endothelium-derived histamine relaxes MLVs. Methods We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat mesenteric lymphatic vessels under control conditions and after pharmacological blockade of nitric oxide by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM) or/and histamine production by α-methyl-DL-histidine dihydrochloride (α-MHD, 10 μM). Effectiveness of α-MHD was confirmed immunohistochemically. We also used immunohistochemical labeling and western blot analysis of the histamine-producing enzyme, histidine decarboxylase (HDC). Additionally we blocked HDC protein expression in MLVs by transient transfection with vivo-morpholino oligos. Results We found that only combined pharmacological blockade of nitric oxide and histamine production completely eliminates flow-dependent relaxation of lymphatic vessels, thus confirming a role for histamine as an EDRF in MLVs. We also confirmed the presence of histidine decarboxylase and histamine inside lymphatic endothelial cells. Conclusions Our study supports a role for histamine as an EDRF in MLVs. PMID:24750494

  6. Endothelium-dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin-sensitive K+ conductance.

    PubMed Central

    García-Pascual, A.; Labadía, A.; Jimenez, E.; Costa, G.

    1995-01-01

    1. Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in bovine oviductal arteries (o.d. 300-500 microns and i.d. 150-300 microns) in vitro. Vascular rings were treated with indomethacin (10 microM) to prevent the effects of prostaglandins. 2. ACh elicited a concentration-related relaxation in ring segments precontracted with noradrenaline (NA), which was abolished by endothelium denudation. 3. The ACh-induced relaxation was attenuated but not abolished by NG-nitro-L-arginine (L-NOARG, 1 microM-1 mM), an inhibitor of nitric oxide (NO) formation. The inhibition caused by L-NOARG (10 microM) was reversed by addition of excess of L-arginine but not D-arginine (1 mM). 4. In high K+ (40-60 mM)-contracted rings, ACh was a much less effective vasodilator and its relaxant response was completely abolished by L-NOARG (100 microM). 5. In NA (10 microM)-contracted rings, ACh induced sustained and concentration-dependent increases in cyclic GMP, which were reduced below basal values by L-NOARG (100 microM), while potent relaxation persisted. Similar increases in cyclic GMP were evoked by ACh in high K+ (50 mM)-treated arteries and under these conditions, both cyclic GMP accumulation and relaxation were L-NOARG-sensitive. 6. S-nitroso-L-cysteine (NC), a proposed endogenous precursor of endothelial NO, also induced cyclic GMP accumulation in NA-contracted oviductal arteries. 7. Methylene blue (MB, 10 microM), a proposed inhibitor of soluble guanylate cyclase, inhibited both endothelium-dependent relaxation to ACh and endothelium-independent response to exogenous NO, whereas relaxation to NC remained unaffected. 8. The L-NOARG-resistant response to ACh was not affected by either ouabain (0.5 mM), glibenclamide (3 microM), tetraethylammonium (TEA, 1 mM) or charybdotoxin (50 nM), but was selectively blocked by apamin (0.1-1 microM). However, apamin did not inhibit either relaxation to ACh in high K(+)-contracted rings or endothelium

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

    PubMed Central

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

    2015-01-01

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

  8. The impairment of endothelium-dependent arterial relaxation by7-ketocholesterol is associated with an early activation of protein kinase C

    PubMed Central

    Deckert, Valérie; Duverneuil, Linda; Poupon, Sandrine; Monier, Serge; Le Guern, Naig; Lizard, Gérard; Masson, David; Lagrost, Laurent

    2002-01-01

    Among components of oxidized low density lipoproteins, cholesterol derivatives oxidized in position 7 inhibit endothelium-dependent arterial relaxation by decreasing the release of the main endothelium-derived relaxing factor, nitric oxide (NO). The aim of the present study was to bring new insights into the molecular mechanism by which 7-ketocholesterol can block the endothelium-dependent arterial relaxation. Superoxide dismutase did not prevent the inhibitory effect of 7-ketocholesterol on endothelium-dependent relaxation, and consistent observations were made whether superoxide dismutase was conjugated or not to polyethylene glycol. In addition, neither glutathione supplementation, nor oxypurinol, i.e. a xanthine oxidase inhibitor could reverse the effect of 7-ketocholesterol, indicating that NO was not inactivated by superoxide anion. A direct alteration of the activity of the calcium-dependent NO synthase could also be ruled out, since identical relaxing effects of the calcium ionophore A23187 were observed whether arterial rings were treated or not with 7-ketocholesterol. Whereas the above observations come in support of an early, inhibitory action of 7-ketocholesterol, the specific blockade of one given subtype of membrane receptors could be discarded, and similar inhibitions were observed when either muscarinic or purinergic receptors were stimulated. Finally, the blockade of protein kinase C activity by chelerythrine arose as the sole relevant tool in preventing the effect of 7-ketocholesterol on the endothelium-dependent relaxation of rabbit aortic rings. In addition, complementary studies on cultured bovine aortic endothelial cells came in direct support of the ability of 7-ketocholesterol to activate PKC. In conclusion, 7-ketocholesterol that is present in human hypercholesterolaemic plasma, in atherosclerotic arteries, and in many processed foods can block the release of NO by vascular endothelial cells through its ability to activate PKC. PMID

  9. Endothelium-dependent relaxation and hyperpolarization evoked by bradykinin in canine coronary arteries: enhancement by exercise-training.

    PubMed Central

    Mombouli, J. V.; Nakashima, M.; Hamra, M.; Vanhoutte, P. M.

    1996-01-01

    bradykinin were also shifted to the left by perindoprilat. The shift induced by the ACE-inhibitor in either type of preparation was not significantly different. 8. These findings demonstrate that exercise-training augments the sensitivity of the coronary artery of the dog to the endothelium-dependent effects of bradykinin. This sensitization to bradykinin may reflect an increased role of both NO and EDHF, and is not the consequence of differences in ACE activity in the receptor compartment. PMID:8821528

  10. Role of membrane potential in endothelium-dependent relaxation of guinea-pig coronary arterial smooth muscle.

    PubMed

    Parkington, H C; Tonta, M A; Coleman, H A; Tare, M

    1995-04-15

    1. Membrane potential and tension were measured simultaneously in ring segments of main coronary artery of guinea-pigs. The synthetic thromboxane A2 analogue U46619 depolarized the tissues from -58 +/- 2 to -40 +/- 1 mV and increased tension by 12 +/- 1 mN mm-1. Nitric oxide (NO) and Iloprost, the stable analogue of prostacyclin, evoked hyperpolarization and relaxation. 2. The concentration of NO required to evoke half-maximal hyperpolarization (EC50 of 2 x 10(-5) M) was 40-fold higher than that which was required to induce relaxation (EC50 of 5 x 10(-7) M). The EC50 for Iloprost-induced hyperpolarization (3 x 10(-8) M) was similar to that for relaxation (4 x 10(-8) M). 3. Glibenclamide (10(-6) M) abolished the hyperpolarization in response to both NO and Iloprost but was without effect on the amplitudes of the relaxations over the complete concentration-response curves. 4. Acetylcholine evoked concentration-dependent hyperpolarization and relaxation in the presence of N omega-nitro-L-arginine methyl ester (NAME; 10(-5) M) and indomethacin (10(-6) M), and these responses were attributed to endothelium-derived hyperpolarizing factor (EDHF). The hyperpolarization produced by EDHF always preceded relaxation, and relaxation never occurred at concentrations of acetylcholine that were insufficient to evoke hyperpolarization. 5. The concentration-hyperpolarization and concentration-relaxation curves in response to acetylcholine were not affected by glibenclamide or barium (1-3 mM) but were shifted to the right 4- and 5-fold, respectively, by 1 mM tetraethylammonium. The hyperpolarization and relaxation evoked by acetylcholine were also reduced in a parallel manner when the potassium concentration in the superfusate was increased. 6. Hyperpolarizing current steps, applied to spiral strips of coronary artery denuded of endothelium and depolarized and constricted with U46619, caused relaxation. The relationship between hyperpolarization and relaxation evoked electronically

  11. Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway.

    PubMed

    Wu, Yang; Xue, Lai; Du, Weimin; Huang, Bo; Tang, Cuiping; Liu, Changqing; Qiu, Hongmei; Jiang, Qingsong

    2015-01-01

    Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin's action on vascular endothelial cells (VECs)-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L); however, polydatin (1, 3, 10 μmol/L) could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin's effects were mediated via promoting the expression of endothelial NO synthase (eNOS), enhancing eNOS activity and decreasing the inducible NOS (iNOS) level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARβ signaling pathway. The results provided a novel insight into polydatin action, via PPARβ-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases. PMID:25941823

  12. Chicago sky blue and a helium neon laser abolish endothelium dependent relaxation in vivo in the microcirculation

    SciTech Connect

    Nishimura, H.; Nelson, G.H.; Rosenblum, W.I. )

    1989-12-01

    Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye), resulted in local platelet aggregation at the site of laser impact.

  13. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    PubMed

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

  14. The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

    PubMed Central

    Ribeiro, Êurica Adélia Nogueira; Herculano, Edla de Azevedo; da Costa, Cintia Danieli Ferreira; Furtado, Fabiola Fialho; da-Cunha, Emídio Vasconcelos Leitão; Barbosa-Filho, José Maria; da Silva, Marcelo Sobral; de Medeiros, Isac Almeida

    2012-01-01

    The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy). In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS), indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release. PMID:23346202

  15. 17β-estradiol potentiates endothelium-dependent nitric oxide- and hyperpolarization-mediated relaxations in blood vessels of male but not female apolipoprotein-E deficient mice.

    PubMed

    Kong, Billy W C; Vanhoutte, Paul M; Man, Ricky Y K; Leung, Susan W S

    2015-08-01

    The present study investigated the influence of gender on the changes underlying endothelial dysfunction in hyperlipidemia during aging. Isometric tension in rings (with endothelium) of the aortae and superior mesenteric arteries from apolipoprotein-E deficient mice was determined in wire myographs. Nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations were smaller in the aortae and mesenteric arteries of 32weeks old males than eight weeks old males. In females, NO- and EDH-mediated relaxations were impaired only at 84weeks of age. The levels of reactive oxygen species were elevated in the blood vessels of 32weeks old males, but not females. Acute in vitro treatment with 17β-estradiol and apocynin improved NO- and EDH-mediated relaxations in 32weeks old males but not in 84weeks old males. Relaxations to SKA-31, activator of intermediate (IKCa) and small (SKCa) conductance calcium-activated potassium channels, were attenuated in the mesenteric arteries of 32weeks old males. Such impairment was restored by acute treatment with apocynin. These findings suggest that male hyperlipidemic mice develop endothelial dysfunction at an earlier age than females. This endothelial dysfunction is associated with impaired NO bioavailability and reduced IKCa and SKCa activity. Apocynin and 17β-estradiol restore the endothelial function only in younger male animals but not in older male or female animals. PMID:25869512

  16. Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress

    PubMed Central

    Ali, Saher F.; Woodman, Owen L.

    2015-01-01

    Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect of α-tocopherol, α-, δ-, and γ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin and α-tocopherol were more effective in the isolated aorta. Tocomin and α-tocopherol restored endothelial function in the presence of oxidant stress but α-, δ-, and γ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without, α-tocopherol. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function. PMID:26075031

  17. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    PubMed

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  18. Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit.

    PubMed

    Berhane, Y; Bailey, S R; Putignano, C; Elliott, J

    2008-02-01

    The role of endothelium-derived relaxing factors was studied in the regulation of vascular responses in the Krebs perfused equine isolated digit. Perfusion pressure was recorded in response to bolus doses of 5-hydroxytryptamine (6 nmol) alone or co-administered with carbachol (CCh; 0.2 micromol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 micromol). N(omega)-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 microm) caused partial but significant inhibition of CCh-induced vasodilatory response, whereas BK and SP-induced responses were resistant to L-NAME. High potassium (K(+), 30 mm) and the cytochrome P-450 (CYP) epoxygenase inhibitor, clotrimazole (10 microm) plus L-NAME (100 microm), completely abolished the CCh, BK and SP-induced vasodilatory responses, whereas the response to SNP was unaffected. In contrast, the L-NAME-resistant proportion of CCh, BK and SP-induced vasodilatory response was not inhibited by the highly selective CYP2C9 inhibitor, sulphaphenazole (10 microm). The cyclo-oxygenase inhibitor, ibuprofen (10 microm) did not affect the CCh, BK and SP-induced responses. These data demonstrate that CCh, BK and SP-induced relaxation in the equine digit involve a combination of the NO and endothelium-derived hyperpolarizing factor (EDHF) pathways. These results do not support the evidence for the involvement of CYP-derived epoxyeicosatrienoic acids and the exact nature of EDHF in the equine digit remains to be established. PMID:18177312

  19. Hyperoxic gassing with Tiron enhances bradykinin-induced endothelium-dependent and EDH-type relaxation through generation of hydrogen peroxide.

    PubMed

    Wong, Pui San; Roberts, Richard E; Randall, Michael D

    2015-01-01

    Oxygenation with 95%O2 is routinely used in organ bath studies. However, hyperoxia may affect tissue responses, particularly in studies which involve reactive oxygen species (ROS). Here, the effects of the antioxidant, Tiron, were investigated under different gassing conditions in the porcine isolated coronary artery (PCA). Distal PCAs from male and female pigs were mounted in a wire myograph gassed with either 95%O2/5%CO2 or 95% air/5%CO2 and pre-contracted with U46619. Concentration-response curves to bradykinin were constructed in the presence of Tiron (1mM), a cell permeable superoxide scavenger and catalase (1000Uml(-1)) to breakdown H2O2. The H2O2 level in Krebs'-Henseleit solution was detected using Amplex Red. Bradykinin produced concentration-dependent vasorelaxations in male and female PCAs when gassed with either 95%O2 or air, with no differences in the Rmax or EC50. Tiron increased the potency of bradykinin only when gassed with 95%O2 in PCAs from both sexes. At 95%O2, catalase prevented the leftward shift caused by Tiron in both sexes indicating that catalase prevented the formation of H2O2 by Tiron. In female PCAs, addition of catalase to Tiron significantly reduced the Rmax. In the EDH-type response (using L-NAME and indomethacin), Tiron enhanced the potency of the bradykinin-induced vasorelaxation when gassed with 95%O2 in PCAs from both sexes. Biochemical analysis using Amplex Red demonstrated that H2O2 was generated in Krebs'-Henseleit solution when gassed with 95%O2, but not with air. Therefore, hyperoxic gassing conditions could alter the environment generating superoxide within the Krebs'-Henseleit buffer, which may, in turn, influence the in vitro pharmacological responses. PMID:25450247

  20. Developmental changes in endothelium-dependent pulmonary vasodilatation in pigs.

    PubMed Central

    Liu, S. F.; Hislop, A. A.; Haworth, S. G.; Barnes, P. J.

    1992-01-01

    1. We compared in vitro endothelium-dependent vasorelaxant responses to acetylcholine (ACh) and the endothelium-independent vasodilator response to sodium nitroprusside (SNP) in prostaglandin F2 alpha (PGF2 alpha)-precontracted muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3-10 days, 3-8 weeks and adults. 2. In the pulmonary artery (PA) rings from neonatal animals, the vasodilator response to ACh was negligible. However, responses to ACh were present in all PA rings from older animals, being greatest at 3-10 days and then decreasing with age (P less than 0.001, ANOVA). ACh (30 microM) induced a 1 +/- 1%, 92 +/- 9%, 62 +/- 5% and 51 +/- 6% reduction of the PGF2 alpha-generated tension in neonatal, 3-10 days, 3-8 weeks and adult groups, respectively. 3. The relaxant response to SNP was present in the PA rings from all age groups and increased with age (P less than 0.001, ANOVA). SNP (1 microM)-induced relaxation was 55 +/- 9%, 73 +/- 7%, 97 +/- 5% and 93 +/- 6% in neonatal, 3-10 days, 3-8 week and adult groups, respectively. 4. Removal of the vascular endothelium abolished the relaxant response to ACh but had no effect on the response to SNP in any groups. 5. NG-monomethyl-L-arginine (30 microM), a nitric oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on responses to ACh or SNP in any group.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:1393265

  1. Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway.

    PubMed

    Choi, Sujeong; Kwon, Hyon-Jo; Song, Hee-Jung; Choi, Si Wan; Nagar, Harsha; Piao, Shuyu; Jung, Saet-Byel; Jeon, Byeong Hwa; Kim, Dong Woon; Kim, Cuk-Seong

    2016-09-01

    Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function. PMID:27610041

  2. Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway

    PubMed Central

    Choi, Sujeong; Kwon, Hyon-Jo; Song, Hee-Jung; Choi, Si Wan; Nagar, Harsha; Piao, Shuyu; Jung, Saet-byel; Jeon, Byeong Hwa

    2016-01-01

    Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function. PMID:27610041

  3. Endothelium-Dependent Hyperpolarization and Endothelial Dysfunction.

    PubMed

    Félétou, Michel

    2016-05-01

    The endothelium controls vascular tone not only by releasing various vasoactive substances but also by another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells and is termed endothelium-dependent hyperpolarization (EDH). These responses involve an increase in the endothelial intracellular Ca concentration by the activation of transient receptor potential channels (predominantly TRPV4) followed by the opening of Ca-activated K channels of small and intermediate conductance (SKCa and IKCa). These channels show a distinct subcellular distribution. SKCa are widely distributed over the plasma membrane but segregates at sites of homocellular endothelial junctions, whereas IKCa are preferentially expressed in the myoendothelial projections. Following KCa activation, smooth muscle hyperpolarization is evoked by electrical coupling through myoendothelial gap junctions and/or by the potassium efflux that subsequently activates smooth muscle Kir2.1 and/or Na/K-ATPase. Alteration of the EDH contributes to the endothelial dysfunctions observed in various pathologies or conversely compensates for the loss in NO bioavailability. A better characterization of EDH should allow determining whether new druggable targets can be identified for the treatment of cardiovascular diseases. PMID:26657714

  4. Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endothelium-dependent vasodilation

    PubMed Central

    Soloviev, Anatoly I; Tishkin, Sergey M; Parshikov, Alexander V; Ivanova, Irina V; Goncharov, Eugene V; Gurney, Alison M

    2003-01-01

    Gamma radiation impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about radiation effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rabbits subjected to whole-body irradiation from a cobalt60 source. The endothelium-dependent relaxation of rabbit aorta evoked by acetylcholine (ACh) or A23187 was impaired in a dose-dependent manner by irradiation at 2 Gy or above. Inhibition was evident 9 days post-irradiation and persisted over the 30 day experimental period. Endothelium-independent responses to glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1) were suppressed over a similar dose range at 7–9 days post-irradiation, but recovered fully by 30 days post-irradiation. In healthy vessels, ACh-induced relaxation was inhibited by L-Nω-nitroarginine (L-NA; 3×10−4 M) and charybdotoxin (10−8 M) plus apamin (10−6 M) but resistant to indomethacin, indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). Supporting this, ACh caused smooth muscle hyperpolarization that was reduced by L-NA and charybdotoxin plus apamin. In irradiated vessels, responses to ACh were insensitive to L-NA but abolished by charybdotoxin plus apamin, indicating selective loss of NO-mediated relaxation. In animals treated shortly after irradiation with the antioxidant, α-tocopherol acetate, the NO-dependent relaxation was restored without effect on the EDHF-dependent component. The results imply that radiation selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level. PMID:12642385

  5. Acute effect of rosiglitazone on relaxation responses in hypercholesterolemic corpus cavernosum.

    PubMed

    Akdag, H; Murat, N; Evcim, S; Esen, A; Gidener, S

    2016-05-01

    Thiazolidinediones (TZDs) improve vascular endothelial dysfunction through non-genomic effects of peroxisomal proliferator-activated receptor γ. This study investigated the acute effect of one of the TZD, rosiglitazone, on endothelium-dependent relaxation response of corpus cavernosum (CC) in hypercholesterolemic rabbits. New Zealand rabbits were divided into two groups randomly as control and cholesterol groups. Hypercholesterolemia was induced by feeding rabbits with 2% cholesterol diet (w/w) for 6 weeks. Endothelium-dependent and -independent relaxation response of CC were evaluated in the presence of rosiglitazone by organ bath studies with cumulative doses of acetylcholine (Ach) and sodium nitroprusside (SNP). Maximal relaxation (Emax) response to Ach significantly decreased owing to hypercholesterolemia in CC tissues. However, in vitro incubation of rosiglitazone with different concentrations (0.1, 1 and 10 μm) did not improve the Ach-dependent Emax responses in hypercholesterolemic rabbit CC. Surprisingly, rosiglitazone caused a significant decrease in Ach-dependent relaxation in healthy CC. Emax responses to SNP did not differ in the presence of rosiglitazone in both the control and hypercholesterolemic groups. Rosiglitazone does not improve hypercholesterolemia-induced endothelial dysfunction in CC tissues while it dose-dependently impairs endothelium-dependent relaxation in healthy CC tissue. PMID:27030054

  6. Role of Endothelium-Dependent Hyperpolarisation and Prostacyclin in Diabetes

    PubMed Central

    MOKHTAR, Siti Safiah; RASOOL, Aida Hanum Ghulam

    2015-01-01

    The endothelium plays a crucial role in maintaining vascular homeostasis by producing several vasodilating factors, including nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarisation (EDH); however, the balance between endothelial relaxing and contracting factors is disrupted in disease states such as diabetes mellitus and hypertension. Most reported studies of endothelial dysfunction in diabetes focused on the actions of NO; however, there is accumulating evidence demonstrating that in addition to NO, PGI2 and EDH are likely to contribute to the vasodilatation of blood vessels. EDH plays an important role as a regulator of vascular tone and reactivity in resistance and conduit arteries of animal models and humans. PGI2 only plays a minimal role in endothelium-dependent vasodilatation but may serve as an important compensatory mechanism in conditions in which NO and EDH activities are decreased. Further studies are needed to determine the exact roles of EDH and PGI2 in the development of endothelial dysfunction and clinical vasculopathy in humans with type 1 and type 2 diabetes. PMID:26023290

  7. Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles

    PubMed Central

    LeBlanc, AJ; Cumpston, JL; Chen, BT; Frazer, D; Castranova, V; Nurkiewicz, TR

    2009-01-01

    Exposure to fine particulate matter (PM, mean aerodynamic diameter ≤ 2.5 μm) has been shown to be a risk factor for cardiovascular disease mortality and may contribute to acute coronary events such as myocardial infarction (MI). There is sufficient reason to believe that smaller particles, such as nanoparticles, might be even more detrimental than larger-sized particles due to their increased surface area and higher pulmonary deposition. Our lab showed that nanoparticle inhalation impairs endothelium-dependent arteriolar vasodilation in skeletal muscle. However, it is not known if coronary microvascular endothelial function is affected in a similar manner. Rats were exposed to filtered air (control) or TiO2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations that produced measured depositions (10 μg) relevant to ambient air pollution. Subepicardial arterioles (~150 μm in diameter) were isolated and responses to transmural pressure, flow-induced dilation (FID), acetylcholine, the Ca2+ ionophore A23187, and sodium nitroprusside (SNP) assessed. Myogenic responsiveness was preserved between groups. In addition, there was no difference in the vasodilation to SNP, signifying that smooth muscle sensitivity to nitric oxide (NO) is unaffected by nano-TiO2 exposure. However, inhalation of nano-TiO2 produced an increase in spontaneous tone in coronary arterioles and also impaired endothelium-dependent FID. In addition, ACh- and A23187-induced vasodilation was also blunted in arterioles after inhalation of nano-TiO2. Data showed that nanoparticle exposure significantly impairs endothelium-dependent vasodilation in subepicardial arterioles. Such disturbances in coronary microvascular function are consistent with the cardiac events associated with particle pollution exposure. PMID:20077232

  8. 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

  9. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.

    PubMed

    Ting, H H; Timimi, F K; Boles, K S; Creager, S J; Ganz, P; Creager, M A

    1996-01-01

    Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C (P = 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes. PMID:8550838

  10. Muscarinic Receptor Activation Affects Pulmonary Artery Contractility in Sheep: The Impact of Maturation and Chronic Hypoxia on Endothelium-Dependent and Endothelium-Independent Function.

    PubMed

    Giang, Michael; Papamatheakis, Demosthenes G; Nguyen, Dan; Paez, Ricardo; Blum Johnston, Carla; Kim, Joon; Brunnell, Alexander; Blood, Quintin; Goyal, Ravi; Longo, Lawrence D; Wilson, Sean M

    2016-06-01

    Giang, Michael, Demosthenes G. Papamatheakis, Dan Nguyen, Ricardo Paez, Carla Blum Johnston, Joon Kim, Alexander Brunnell, Quintin Blood, Ravi Goyal, Lawrence D. Longo, and Sean M. Wilson. Muscarinic receptor activation affects pulmonary artery contractility in sheep: the impact of maturation and chronic hypoxia on endothelium-dependent and endothelium-independent function. High Alt Med Biol. 17:122-132, 2015.-Muscarinic receptor activation in the pulmonary vasculature can cause endothelium-dependent vasodilation and smooth muscle-dependent vasoconstriction. Chronic hypoxia (CH) can modify both of these responses. This study aimed to assess the combined influence of CH and maturation on endothelium-dependent and endothelium-independent muscarinic-induced vasoreactivity. This was accomplished by performing wire myography on endothelium-intact or endothelium-disrupted pulmonary arterial rings isolated from normoxic or CH fetal and adult sheep. In endothelium-intact arteries, vasodilation was evaluated using cumulative bradykinin doses in phenylephrine and carbachol precontracted pulmonary arterial segments; and vasoconstriction was examined using cumulative doses of carbachol following bradykinin predilation. Effects of nonselective (atropine) and selective M1 (pirenzepine), M2 (AFDX116), and M3 (4-DAMP and Dau5884) muscarinic receptor antagonists were assessed in disrupted arteries. In normoxic arteries, bradykinin relaxation was twofold greater in the adult compared to fetus, while carbachol contraction was fourfold greater. In adult arteries, CH increased bradykinin relaxation and carbachol contraction. In vessels with intact endothelium, maturation and CH augmented maximal response and efficacy for carbachol constriction and bradykinin relaxation. Approximately 50%-80% of adult normoxic and CH endothelium-disrupted arteries contracted to acetylcholine, while ∼50% of fetal normoxic and ∼10% of CH arteries responded. Atropine reduced carbachol

  11. Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

    PubMed Central

    SUN, Tao; LIU, Rui; CAO, Yong-xiao

    2011-01-01

    Aim: To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods: Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results: Formononetin (1–300 μmol/L) elicited relaxation in arteries of the five regions that were pre-contracted by KCl (60 mmol/L), U46619 (1 μmol/L) or phenylephrine (10 μmol/L). The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME (100 μmol/L). Under conditions of endothelium denudation, formononetin (10, 30, and 100 μmol/L) inhibited the contraction induced by KCl and that induced by CaCl2 in Ca2+-free depolarized medium. In the absence of extracellular Ca2+, formononetin (10, 30, and 100 μmol/L) depressed the constriction caused by phenylephrine (10 μmol/L), but did not inhibit the tonic contraction in response to the addition of CaCl2 (2 mmol/L). The contraction caused by caffeine (30 mmol/L) was not inhibited by formononetin (100 μmol/L). Formononetin (10 and 100 μmol/L) reduced the change rate of Ca2+-fluorescence intensity in response to KCl (50 mmol/L). In spontaneously hypertensive rats, formononetin (5, 10, and 20 mg/kg) slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion: Formononetin causes vasodilatation via two pathways: (1) endothelium-independent pathway, probably due to inhibition of voltage-dependent Ca2+ channels and intracellular Ca2+ release; and (2) endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect. PMID:21818108

  12. Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery.

    PubMed

    Baranowska-Kuczko, Marta; MacLean, Margaret R; Kozłowska, Hanna; Malinowska, Barbara

    2012-09-01

    Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)-nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve K(Ca) or the NO pathway. PMID:22627170

  13. Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels

    PubMed Central

    Greenberg, Harry Z.E.; Shi, Jian; Jahan, Kazi S.; Martinucci, Matthew C.; Gilbert, Steven J.; Vanessa Ho, W.-S.; Albert, Anthony P.

    2016-01-01

    Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K+ channels in these responses. In wire myography studies, increasing [Ca2 +]o from 1 mM to 6 mM induced concentration-dependent relaxations of methoxamine pre-contracted rabbit mesenteric arteries. [Ca2 +]o-induced relaxations were dependent on a functional endothelium, and were inhibited by the negative allosteric CaSR modulator Calhex-231. [Ca2 +]o-induced relaxations were reduced by inhibitors of endothelial NO synthase, guanylate cyclase, and protein kinase G. CaSR activation also induced NO production in freshly isolated endothelial cells (ECs) in experiments using the fluorescent NO indicator DAF-FM. Pre-treatment with inhibitors of large (BKCa) and intermediate (IKCa) Ca2 +-activated K+ channels (iberiotoxin and charybdotoxin), and Kv7 channels (linopirdine) also reduced [Ca2 +]o-induced vasorelaxations. Increasing [Ca2 +]o also activated IKCa currents in perforated-patch recordings of isolated mesenteric artery ECs. These findings indicate that stimulation of CaSRs induces endothelium-dependent vasorelaxations which are mediated by two separate pathways involving production of NO and activation of IKCa channels. NO stimulates PKG leading to BKCa activation in vascular smooth muscle cells, whereas IKCa activity contributes to endothelium-derived hyperpolarisations. PMID:26772767

  14. Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels.

    PubMed

    Greenberg, Harry Z E; Shi, Jian; Jahan, Kazi S; Martinucci, Matthew C; Gilbert, Steven J; Vanessa Ho, W-S; Albert, Anthony P

    2016-05-01

    Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K(+) channels in these responses. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine pre-contracted rabbit mesenteric arteries. [Ca(2+)]o-induced relaxations were dependent on a functional endothelium, and were inhibited by the negative allosteric CaSR modulator Calhex-231. [Ca(2+)]o-induced relaxations were reduced by inhibitors of endothelial NO synthase, guanylate cyclase, and protein kinase G. CaSR activation also induced NO production in freshly isolated endothelial cells (ECs) in experiments using the fluorescent NO indicator DAF-FM. Pre-treatment with inhibitors of large (BKCa) and intermediate (IKCa) Ca(2+)-activated K(+) channels (iberiotoxin and charybdotoxin), and Kv7 channels (linopirdine) also reduced [Ca(2+)]o-induced vasorelaxations. Increasing [Ca(2+)]o also activated IKCa currents in perforated-patch recordings of isolated mesenteric artery ECs. These findings indicate that stimulation of CaSRs induces endothelium-dependent vasorelaxations which are mediated by two separate pathways involving production of NO and activation of IKCa channels. NO stimulates PKG leading to BKCa activation in vascular smooth muscle cells, whereas IKCa activity contributes to endothelium-derived hyperpolarisations. PMID:26772767

  15. Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery.

    PubMed

    Denniss, Steven G; Ford, Rebecca J; Smith, Christopher S; Jeffery, Andrew J; Rush, James W E

    2016-05-15

    Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) (P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg(-1)·day(-1) RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg(-1)·day(-1) RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619-stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by

  16. Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults

    PubMed Central

    Eisenach, John H; Gullixson, Leah R; Allen, Alexander R; Kost, Susan L; Nicholson, Wayne T

    2014-01-01

    Aim A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both. Method We tested this hypothesis in 12 younger (age 18–38 years, six women) and 12 older healthy adults (age 55–73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl−1 forearm tissue min−1) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial NG-monomethyl-l arginine acetate (L-NMMA). Results Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups. Conclusion In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors. PMID:24698105

  17. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans.

    PubMed

    Nishioka, Kenji; Hidaka, Takayuki; Nakamura, Shuji; Umemura, Takashi; Jitsuiki, Daisuke; Soga, Junko; Goto, Chikara; Chayama, Kazuaki; Yoshizumi, Masao; Higashi, Yukihito

    2007-09-01

    Pycnogenol, an extract of bark from the French maritime pine, Pinus pinaster Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids. Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO) synthase expression and subsequent NO release from endothelial cells. The purpose of this study was to determine Pycnogenol's effects on endothelium-dependent vasodilation in humans. This was a double-blind, randomized, placebo and active drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol (180 mg/day) (n=8) or placebo (n=8). FBF was measured by using strain-gauge plethysmography. Neither the placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol, but not placebo, augmented FBF response to ACh, from 13.1 +/- 7.0 to 18.5 +/- 4.0 mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol groups. The administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, completely abolished Pycnogenol-induced augmentation of the FBF response to ACh. These findings suggest that Pycnogenol augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction. PMID:18037769

  18. Endothelium-dependent vasorelaxation in the aorta of transgenic mice expressing human apolipoprotein(a) or lipoprotein(a).

    PubMed

    Rubanyi, G M; Freay, A D; Lawn, R M

    2000-01-01

    Elevated plasma level of lipoprotein(a) (Lp(a)) is a well established risk factor for premature atherosclerosis and coronary artery disease. Recent studies showed impaired endothelium-dependent vasodilatation in humans with elevated plasma Lp(a). However, these human studies could not determine whether (1) elevated Lp(a) levels alone are the cause of endothelial dysfunction (these patients had multiple risk factors), and (2) native or oxidatively modified Lp(a) contributes to endothelial dysfunction (no measurements of native/oxidized Lp(a) ratio was reported in humans). In order to test whether apo(a) (an essential component of Lp(a) which is required for binding to endothelial cells) and native Lp(a) cause endothelial dysfunction, in the present study we tested endothelium-dependent vasorelaxation in aortic rings isolated from control and transgenic male mice either expressing the human apo(a) gene (TgA) or both the human apo(a) and human apo B100 genes (TgL). The TgA mice had plasma apo(a) levels of 8.8 +/- 1.2 mg/dl (n=6) and the double transgenic TgL mice had plasma Lp(a) levels of 15.3 +/- 1.4 mg/dl (n=8). Isolated aortic rings with and without endothelium were mounted in organ chambers and contracted with U46619 (10(-8) M) in the presence of ibuprofen (10(-5) M). Acetylcholine caused concentration-dependent (10(-9)-10(-5) M) relaxation, which could be prevented by endothelium removal and by NG-L-nitro-arginine (10(-4) M). Basal and acetylcholine-stimulated endothelium-dependent relaxation and endothelium-independent relaxation to nitroglycerin (10(-6) M) were not significantly different in aortic rings isolated from control and TgA or TgL mice. Twenty-four hour incubation of aortic rings isolated from control mice with recombinant human apo(a) or native Lp(a) (up to 300 microg/ml) caused no impairment of endothelium-dependent relaxations. In contrast, incubation with oxidized Lp(a) (50 microg/ml) or oxidized LDL (250 microg/ml) caused significant suppression

  19. The vasorelaxant effect of gallic acid involves endothelium-dependent and -independent mechanisms.

    PubMed

    de Oliveira, Lais Moraes; de Oliveira, Thiago Sardinha; da Costa, Rafael Menezes; de Souza Gil, Eric; Costa, Elson Alves; Passaglia, Rita de Cassia Aleixo Tostes; Filgueira, Fernando Paranaíba; Ghedini, Paulo César

    2016-06-01

    The mechanisms of action involved in the vasorelaxant effect of gallic acid (GA) were examined in the isolated rat thoracic aorta. GA exerted a relaxant effect in the highest concentrations (0.4-10mM) in both endothelium-intact and endothelium-denuded aortic rings. Pre-incubation with L-NAME, ODQ, calmidazolium, TEA, 4-aminopyridine, and barium chloride significantly reduced the pEC50 values. Moreover, this effect was not modified by indomethacin, wortmannin, PP2, glibenclamide, or paxillin. Pre-incubation of GA (1, 3, and 10mM) in a Ca(2+)-free Krebs solution attenuated CaCl2-induced contractions and blocked BAY K8644-induced vascular contractions, but it did not inhibit a contraction induced by the release of Ca(2+) from the sarcoplasmatic reticulum stores. In addition, a Western blot analysis showed that GA induces phosphorylation of eNOS in rat thoracic aorta. These results suggest that GA induces relaxation in rat aortic rings through an endothelium-dependent pathway, resulting in eNOS phosphorylation and opening potassium channels. Additionally, the relaxant effect by an endothelium-independent pathway involves the blockade of the Ca(2+) influx via L-type Ca(2+) channels. PMID:26643780

  20. Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

    PubMed Central

    Stapleton, Phoebe A.; Minarchick, Valerie C.; Cumpston, Amy M.; McKinney, Walter; Chen, Bean T.; Sager, Tina M.; Frazer, David G.; Mercer, Robert R.; Scabilloni, James; Andrew, Michael E.; Castranova, Vincent; Nurkiewicz, Timothy R.

    2012-01-01

    Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. PMID:23203034

  1. Differences in responsiveness of intrapulmonary artery and vein to arachidonic acid: mechanism of arterial relaxation involves cyclic guanosine 3':5'-monophosphate and cyclic adenosine 3':5'-monophosphate

    SciTech Connect

    Ignarro, L.J.; Harbison, R.G.; Wood, K.S.; Wolin, M.S.; McNamara, D.B.; Hyman, A.L.; Kadowitz, P.J.

    1985-06-01

    The objective of this study was to examine the relationship between responses of bovine intrapulmonary artery and vein to arachidonic acid and cyclic nucleotide levels in order to better understand the mechanism of relaxation elicited by arachidonic acid and acetylcholine. Arachidonic acid relaxed phenylephrine-precontracted arterial rings and elevated both cyclic GMP and cyclic AMP levels in arteries with intact endothelium. In contrast, endothelium-damaged arterial rings contracted to arachidonic acid without demonstrating significant changes in cyclic nucleotide levels. Indomethacin partially inhibited endothelium-dependent relaxation and abolished cyclic AMP accumulation whereas methylene blue, a guanylate cyclase inhibitor, partially inhibited relaxation and abolished cyclic GMP accumulation in response to arachidonic acid. All vessel responses were blocked by a combination of the two inhibitors. Prostaglandin (PG) I2 relaxed arterial rings and elevated cyclic AMP levels whereas PGE2 and PGF2 alpha caused contraction, suggesting that the indomethacin-sensitive component of arachidonic acid-elicited relaxation is due to PGI2 formation and cyclic AMP accumulation. The methylene blue-sensitive component is attributed to an endothelium-dependent but cyclooxygenase-independent generation of a substance causing cyclic GMP accumulation. Intrapulmonary veins contracted to arachidonic acid with no changes in cyclic nucleotide levels and PGI2 was without effect. Homogenates of intrapulmonary artery and vein formed 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from (/sup 14/C)arachidonic acid, which was inhibited by indomethacin. Thus, bovine intrapulmonary vein may not possess receptors for PGI2.

  2. An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in healthy subjects.

    PubMed

    Sarabi, M; Fugmann, A; Karlström, B; Berne, C; Lithell, H; Lind, L

    2001-06-01

    This study was designed to evaluate the effects of an ordinary mixed meal on endothelium-dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium-dependent vasodilation and endothelium-independent vasodilation were evaluated by local infusion of metacholine (4 microg min (-1)) and sodium nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium-dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to 13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium-dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium-independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium-dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium-dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function. PMID:11442450

  3. Comparison of endothelium-derived relaxing factor activity between nonpregnant and pregnant rats.

    PubMed

    Honda, H; Kaneko, H; Kondo, M; Kogo, H

    1996-07-01

    The tension of isolated ring preparation of aorta from nonpregnant and pregnant rats was measured isometrically to study the effect of pregnancy on endothelium-derived relaxing factor activity. Contraction in response to norepinephrine and potassium chloride was greater in aortae from nonpregnant rats than in those from pregnant rats. The endothelium-dependent relaxation that was caused by acetylcholine (10(-10)-3 x 10(-9) M) in aortae precontracted with norepinephrine was significantly enhanced in aortae from pregnant rats compared with the relaxation in those from nonpregnant rats. NG-nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium-dependent relaxation in both aorta from pregnant and nonpregnant rats. L-Arginine reversed the inhibition of L-NAME. Those results suggest that the enhanced endothelium-derived relaxing factor activity in rats aortae is associated with pregnancy. PMID:8856958

  4. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

    PubMed Central

    Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

    2015-01-01

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women. PMID:26577845

  5. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats.

    PubMed

    Borgo, M V; Claudio, E R G; Silva, F B; Romero, W G; Gouvea, S A; Moysés, M R; Santos, R L; Almeida, S A; Podratz, P L; Graceli, J B; Abreu, G R

    2016-01-01

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women. PMID:26577845

  6. Reduced agonist-induced endothelium-dependent vasodilation in uremia is attributable to an impairment of vascular nitric oxide.

    PubMed

    Passauer, Jens; Pistrosch, Frank; Büssemaker, Eckhart; Lässig, Grit; Herbrig, Kay; Gross, Peter

    2005-04-01

    Current concepts for the explanation of endothelial dysfunction and accelerated atherosclerosis in uremia propose a reduced vascular bioavailability of nitric oxide (NO). The aim of the present study was to test the contributions of NO and NO/prostacyclin (PGI(2))-independent mechanisms to both baseline vascular tone and agonist-induced endothelium-dependent vasodilation in patients on hemodialysis (HD). In 10 HD patients and eight matched healthy control subjects, forearm blood flow (FBF) was measured at rest and during intrabrachial infusions of norepinephrine (NE; endothelium-independent vasoconstrictor, 60, 120, and 240 pmol/min) and N-monomethyl-L-arginine (blocker of NO synthases, 16 micromol/min). After inhibition of cyclo-oxygenase by ibuprofen (1200 mg orally), endothelium-dependent and -independent vasodilation was assessed by infusion of acetylcholine (ACh; 1, 5, 10, 50, 100, and 300 nmol/min) and sodium-nitroprusside (2.5, 5, and 10 microg/min). NO/PGI(2)-independent vasodilation was tested by equal infusions of ACh during NO clamp. N-monomethyl-L-arginine reduced resting FBF to a comparable degree in both groups. Vascular responses to ACh were reduced in HD (P = 0.003 versus control by ANOVA), whereas those to sodium nitroprusside were mainly at control level. Infusion of ACh during NO clamp caused a similar increment of FBF in both groups. NO-mediated vasodilation as calculated by the difference between ACh-induced responses without and with NO clamp was substantially impaired in HD (P < 0.001) compared with control. In HD patients, baseline NO-mediated arteriolar tone is at control level. This study provides first evidence that endothelial dysfunction of uremic patients as shown by reduced agonist-induced endothelium-dependent vasodilation is attributable to reduced stimulation of NO, whereas the NO/PGI(2)-resistant portion of ACh-mediated vasodilation is unaffected. PMID:15728785

  7. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

    PubMed Central

    2014-01-01

    Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions. PMID:25343007

  8. The involvement of the endothelium in the relaxation of the leopard frog (Rana pipiens) aorta in response to acetylcholine.

    PubMed Central

    Knight, G. E.; Burnstock, G.

    1996-01-01

    1. The vasodilator response to acetylcholine (ACh) was investigated in the aortic arches of the leopard frog (Rana pipiens). 2. With adrenaline pre-constricted preparations, both ACh and sodium nitroprusside (SNP) caused concentration-dependent relaxations. Damage to the endothelial layer abolished relaxations to ACh, or reduced them greatly, but had no effect on vasodilatation to SNP. 3. NG-Nitro-L-arginine methyl ester (L-NAME; 1-100 microM) concentration-dependently inhibited relaxations in response to ACh, but had no effect on the ability of SNP to induce vasodilatation. 4. L-Arginine (L-Arg; 100-200 times the concentration of L-NAME) failed to reverse the inhibitory effect of L-NAME (1-100 microM) apart from one isolated instance. 5. In summary, this study has shown endothelium-dependent vasodilatation to ACh in an amphibian blood vessel that appears to be mediated via nitric oxide (NO). The response to ACh differs from many mammalian preparations in that the inhibitory effect of L-NAME could not be overcome by L-Arg, in addition to L-NAME itself having no direct effect upon the tone of the vessel. PMID:8832080

  9. Sex differences in the role of transient receptor potential (TRP) channels in endothelium-dependent vasorelaxation in porcine isolated coronary arteries.

    PubMed

    Wong, Pui San; Roberts, Richard E; Randall, Michael D

    2015-03-01

    Endothelial and smooth muscle Transient Receptor Potential (TRP) channels contribute to regulation of vascular tone. We have previously reported sex differences in the endothelial function in porcine isolated coronary arteries (PCAs). The present study examined the role of TRP channels in endothelium-dependent and H2O2-induced vasorelaxations in male and female PCAs. Distal PCAs were mounted in a wire myograph and precontracted with U46619. Concentration-response curves to bradykinin, H2O2 and A23187 were constructed in the presence of TRP channel antagonists with or without L-NAME and indomethacin to inhibit NO synthase and cyclooxygenase respectively. 2-APB (TRPC & TRPM antagonist) inhibited the maximum relaxation (Rmax) of the bradykinin-induced vasorelaxation and abolished the EDH-type response in PCAs from both sexes. SKF96365 (TRPC antagonist) inhibited the Rmax of bradykinin-induced vasorelaxation in males, and inhibited Rmax of the EDH-type response in both sexes. Pyr3 (TRPC3 antagonist) inhibited both the NO and EDH components of the bradykinin-induced vasorelaxation in males, but not females. RN1734 (TRPV4 antagonist) reduced the potency of the NO component of the bradykinin-induced vasorelaxation in females only, but inhibited the Rmax of the EDH-type component in both sexes. 2-APB, SKF96365 and RN1734 all reduced the H2O2-induced vasorelaxation, whereas Pyr3 had no effect. No differences in expression level of TRPC3 and TRPV4 between sexes were detected using Western blot. Present study demonstrated a clear sex differences in the role TRP channels where TRPC3 play a role in the NO- and EDH-type response in males and TRPV4 play a role in the NO-mediated response in females. PMID:25620134

  10. Serum alkaline phosphatase negatively affects endothelium-dependent vasodilation in naïve hypertensive patients.

    PubMed

    Perticone, Francesco; Perticone, Maria; Maio, Raffaele; Sciacqua, Angela; Andreucci, Michele; Tripepi, Giovanni; Corrao, Salvatore; Mallamaci, Francesca; Sesti, Giorgio; Zoccali, Carmine

    2015-10-01

    Tissue nonspecific alkaline phosphatase, promoting arterial calcification in experimental models, is a powerful predictor of total and cardiovascular mortality in general population and in patients with renal or cardiovascular diseases. For this study, to evaluate a possible correlation between serum alkaline phosphatase levels and endothelial function, assessed by strain gauge plethysmography, we enrolled 500 naïve hypertensives divided into increasing tertiles of alkaline phosphatase. The maximal response to acetylcholine was inversely related to alkaline phosphatase (r=−0.55; P<0.001), and this association was independent (r=−0.61; P<0.001) of demographic and classical risk factors, body mass index, estimated glomerular filtration rate, serum phosphorus and calcium, C-reactive protein, and albuminuria. At multiple logistic regression analysis, the risk of endothelial dysfunction was ≈3-fold higher in patients in the third tertile than that of patients in the first tertile. We also tested the combined role of alkaline phosphatase and serum phosphorus on endothelial function. The steepness of the alkaline phosphatase/vasodilating response to acetylcholine relationship was substantially attenuated (P<0.001) in patients with serum phosphorus above the median value when compared with patients with serum phosphorus below the median (−5.0% versus −10.2% per alkaline phosphatase unit, respectively), and this interaction remained highly significant (P<0.001) after adjustment of all the previously mentioned risk factors. Our data support a strong and significant inverse relationship between alkaline phosphatase and endothelium-dependent vasodilation, which was attenuated by relatively higher serum phosphorus levels. PMID:26324506

  11. Anomalous relaxation and dielectric response

    NASA Astrophysics Data System (ADS)

    Goychuk, Igor

    2007-10-01

    It is shown that all the known experimental (quasi)stationary dielectric response functions of glassy media can be derived from a standard generalized Langevin description of overdamped torsional dipole oscillators in trapping potentials with random orientations under some minimal assumptions. The non-Markovian theory obeys the fluctuation-dissipation theorem and the Onsager regression theorem. Moreover, it displays no aging on the time scale of the dielectric response, all in assumption of local thermal (quasi)equilibrium. Aging might come from jumping among metastable traps. It occurs on a quite different time scale which is not related to the principal dielectric response. We put the old phenomenological theory of Cole and Cole, Davidson and Cole, and others on a firm basis within a stochastic, thermodynamically consistent approach.

  12. Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction

    PubMed Central

    Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

    2012-01-01

    Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, ‘premature’ vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using ‘endothelial therapy’ aiming at maintaining or restoring vascular endothelial health. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21557734

  13. Low-intensity voluntary running lowers blood pressure with simultaneous improvement in endothelium-dependent vasodilatation and insulin sensitivity in aged spontaneously hypertensive rats.

    PubMed

    Sun, Meng-Wei; Qian, Feng-Lei; Wang, Jian; Tao, Tao; Guo, Jing; Wang, Lie; Lu, Ai-Yun; Chen, Hong

    2008-03-01

    Our objective is to examine the effects of voluntary running at different intensity levels on blood pressure, endothelium-dependent vessel dysfunction and insulin resistance in aged spontaneously hypertensive rats (SHR) with severe hypertension. Ten-month-old male and female SHR with severe hypertension were assigned to voluntary running at either low intensity (30% of maximal aerobic velocity) or moderate intensity (60% of maximal aerobic velocity) on a motor-driven treadmill for 6 weeks, 20 min per day and 7 days per week. Age-matched Wistar-Kyoto rats and SHR were kept under sedentary conditions as controls. Blood pressure and heart rate were measured by the tail-cuff method. At the end of the exercise training, blood samples were collected for glucose, insulin and lipids assay, and aortae were isolated to examine their function in vitro. Low-intensity but not moderate-intensity running significantly lowered blood pressure in both male and female SHR (p<0.01). There was significant impairment in acetylcholine-induced vasorelaxation in SHR (p<0.01), which was improved by low-intensity training (p<0.05). Nitric oxide synthase blockade abrogated the improvement in endothelium-dependent relaxation. Hypertensive rats had elevated blood glucose and insulin levels with lowered insulin sensitivity that was ameliorated by low-intensity running. A significant increase in blood high-density lipoprotein (HDL)-cholesterol and a significant decrease in triglycerides were found in exercised SHR. In conclusion, low-intensity voluntary exercise lowers hypertension in aged SHR with severe hypertension. Exercise-induced simultaneous improvement in endothelium-dependent vessel relaxation and insulin sensitivity may act concomitantly in attenuating cardiovascular risk factors in aged hypertensive rats with significantly high blood pressure. PMID:18497475

  14. Role of different types of potassium channels in the relaxation of corpus cavernosum induced by resveratrol

    PubMed Central

    Dalaklioglu, Selvinaz; Ozbey, G.

    2014-01-01

    Background: Resveratrol (RVT), one of the most commonly employed dietary polyphenol, is used in traditional Japanese and Chinese medicine for treatment of cardiovascular diseases. Recently, we have shown that RVT has a potent relaxant effect on rat corpus cavernosum via endothelium-dependent and -independent mechanisms. Objective: The present study addressed the question whether different types of potassium channels are involved in the endothelium-dependent and -independent mechanism of corpus cavernosum relaxation induced by RVT. Materials and Methods: Strips of corpus cavernosum from rats were mounted in an organ-bath system for isometric tension studies. Results: RVT (1-100 μmol/L) produced concentration-dependent relaxation responses in rat corpus cavernosum pre-contracted by phenylephrine. The non-selective potassium channels blocker tetraethylammonium chloride (TEA, 10 mmol/L), ATP-sensitive potassium (KATP) channels blocker glibenclamide (10 μmol/L), and inward rectifier potassium (Kir) channels inhibitor barium chloride (BaCl2, 30 μmol/L) caused a significant inhibition on the relaxation response to RVT, whereas voltage-dependent potassium channels inhibitor 4-aminopyridine (4-AP, 1 mmol/L), and large conductance calcium-activated potassium (BKCa) channels inhibitor iberiotoxin (IbTX, 0.1 μmol/L) did not significantly alter relaxant responses of corpus cavernosum strips to RVT. In addition, relaxant responses to RVT did not significantly inhibited by the combination of selective inhibitors of small and intermediate conductance BKCa channels (0.1 μmol/L charybdotoxin and 1 μmol/L apamin, respectively). Conclusion: These results demonstrated that endothelial small and intermediate conductance BKCa channels are not thought to be an important role in RVT-induced endothelium-dependent relaxation of corpus cavernosum. The endothelium-independent corpus cavernosum relaxation induced by RVT is seems to largely depend on Kir channels and KATP channels in

  15. Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

    PubMed Central

    Madlala, Hlengiwe P.; Metzinger, Thomas; van Heerden, Fanie R.; Mubagwa, Kanigula; Dessy, Chantal

    2016-01-01

    Purpose Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C. Methods Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors. Results OA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation. Conclusion These data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart. PMID:26799746

  16. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    PubMed Central

    Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2015-01-01

    The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

  17. Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles.

    PubMed

    Matin, Nusrat; Fisher, Courtney; Jackson, William F; Dorrance, Anne M

    2016-05-15

    Chronic cerebral hypoperfusion is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral carotid artery stenosis (BCAS) is a physiologically relevant model of chronic cerebral hypoperfusion. We hypothesized that BCAS in 20-wk-old Wistar-Kyoto (WKY) rats would impair cognitive function and lead to reduced endothelium-dependent dilation and outward remodeling in the parenchymal arterioles (PAs). After 8 wk of BCAS, both short-term memory and spatial discrimination abilities were impaired. In vivo assessment of cerebrovascular reserve capacity showed a severe impairment after BCAS. PA endothelial function and structure were assessed by pressure myography. BCAS impaired endothelial function in PAs, as evidenced by reduced dilation to carbachol. Addition of nitric oxide synthase and cyclooxygenase inhibitors did not change carbachol-mediated dilation in either group. Inhibiting CYP epoxygenase, the enzyme that produces epoxyeicosatrienoic acid (EETs), a key determinant of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation, abolished dilation in PAs from Sham rats, but had no effect in PAs from BCAS rats. Expression of TRPV4 channels, a target for EETs, was decreased and maximal dilation to a TRPV4 agonist was attenuated after BCAS. Together these data suggest that EET-mediated dilation is impaired in PAs after BCAS. Thus impaired endothelium-dependent dilation in the PAs may be one of the contributing factors to the cognitive impairment observed after BCAS. PMID:26968546

  18. Endothelium-dependent vasodilator effects of the extract from Salviae Miltiorrhizae radix. A study on the identification of lithospermic acid B in the extracts.

    PubMed

    Kamata, K; Iizuka, T; Nagai, M; Kasuya, Y

    1993-07-01

    1. The aqueous extract of Salviae Miltiorrhizae radix (Chinese crude drug named "dan-shen") relaxed the noradrenaline-precontracted aorta with endothelium. 2. Vasodilation by the extract disappeared in aorta without endothelium, and was inhibited by pretreatment with 10(-4) M NG-monomethyl-L-arginine (L-NMMA) or 10(-5) M methylene blue. 3. The inhibition of the extract-induced vasodilation by L-NMMA was reversed by L-arginine (3 x 10(-4) M). 4. The component of the extract was analyzed by chromatography, fast atom bombardment mass spectroscopy (FAB-MS) and 1H-NMR. 5. An active component of the extract, which showed endothelium-dependent vasodilation, was found to be identical with lithospermic acid B. PMID:8224751

  19. Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric arteries of female rats in long-term deficiency of oestrogen and during oestrus cycle

    PubMed Central

    Liu, Ming-Yue; Hattori, Yuichi; Fukao, Mistuhiro; Sato, Atsushi; Sakuma, Ichiro; Kanno, Morio

    2001-01-01

    This study was undertaken to determine whether endothelium-dependent relaxations are altered in mesenteric arteries from young female rats during oestrus cycle and after castration. The contractile response to phenylephrine (Phe) was significantly enhanced in arteries from rats subjected to ovariectomy than in those from sham-operated (control) rats. Treatment of ovariectomized rats with 17β-oestradiol returned the Phe response to the control level. Arteries from rats at the diestrus stage also exhibited greater contraction in response to Phe. In the presence of 100 μM NG-nitro-L-arginine (L-NOARG), the enhancement of the Phe contractile response associated with oestrogen deficiency was not observed. Endothelium-dependent relaxations elicited by acetylcholine (ACh) in arteries precontracted with Phe were significantly reduced in ovariectomized and diestrus rats regardless of whether endothelium-derived nitric oxide (NO) was blocked with L-NOARG. Treatment with 17β-oestradiol prevented the reduced vascular relaxant response to ACh in ovariectomized rats. The reduction in the ACh responses observed in ovariectomized and diestrus rats was eliminated when 500 nM apamin and 100 nM charybdotoxin were present. ACh-induced endothelium-dependent hyperpolarizations were depressed in arteries from ovariectomized and diestrus rats. The hyperpolarizing response to ACh was significantly improved when ovariectomized rats were treated with 17β-oestradiol. The resting membrane potentials and pinacidil-induced hyperpolarizations were unaffected by ovariectomy or the diestrus stage. These results suggest that oestrogen-deficient states of both short and long duration reduce the basal release of NO from the endothelium and specifically attenuate endothelium-dependent hyperpolarization and relaxation transduced by endothelium-derived hyperpolarizing factor. PMID:11226134

  20. Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Schrage, W. G.; Rush, J. W.; Ray, C. A.; Price, E. M.; Hasser, E. M.; Laughlin, M. H.

    2001-01-01

    We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

  1. Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta.

    PubMed

    Kaneda, Takeharu; Sasaki, Noriyasu; Urakawa, Norimoto; Shimizu, Kazumasa

    2016-01-01

    This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 μmol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-NG-nitroarginine methyl ester (L-NAME, 100 μmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 μmol/l) increased cGMP contents, significantly and L-NAME (100 μmol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium-denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+]i level. In PE-precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta. PMID:26836124

  2. Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction.

    PubMed

    Bar, Anna; Skórka, Tomasz; Jasiński, Krzysztof; Sternak, Magdalena; Bartel, Żaneta; Tyrankiewicz, Urszula; Chlopicki, Stefan

    2016-08-01

    Endothelial dysfunction is linked to impaired endothelial-dependent vasodilatation and permeability changes. Here, we quantify both of these phenomena associated with endothelial dysfunction by MRI in vivo in mice. Endothelial function was evaluated in the brachiocephalic artery (BCA) and left carotid artery (LCA) in ApoE/LDLR(-/-) and high-fat diet (HFD)-fed mice as compared with control mice (C57BL/6J). The 3D IntraGate® FLASH sequence was used for evaluation of changes in vessels' cross-sectional area (CSA) and volume following acetylcholine (Ach) administration. Evaluation of endothelial permeability after administration of contrast agent (Galbumin, BioPAL) was based on the variable flip angle method for the assessment of parameters based on the relaxation time (T1 ) value. In order to confirm the involvement of nitric oxide (NO) in response to Ach, L-NAME-treated mice were also analyzed. To confirm that endothelial permeability changes accompany the impairment of Ach-dependent vasodilatation, permeability changes were analyzed in isolated, perfused carotid artery. In C57BL/6J mice, Ach-induced vasodilatation led to an approximately 25% increase in CSA in both vessels, which was temporarily dissociated from the effect of Ach on heart rate. In ApoE/LDLR(-/-) or HFD-fed mice Ach induced a paradoxical vasoconstriction that amounted to approximately 30% and 50% decreases in CSA of BCA and LCA respectively. In ApoE/LDLR(-/-) and HFD-fed mice endothelial permeability in BCA was also increased (fall in T1 by about 25%). In L-NAME-treated mice Ach-induced vasodilatation in BCA was lost. In isolated, perfused artery from ApoE/LDLR(-/-) mice endothelial permeability was increased. MRI-based assessment of endothelium-dependent vasodilatation induced by Ach and endothelial permeability using a retrospectively self-gated 3D gradient-echo sequence (IntraGate® FLASH) enables the reliable detection of systemic endothelial dysfunction in mice and provides an important tool

  3. MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway

    PubMed Central

    Zhao, Yang; Dong, Shaoting; Zhang, Jingwen; Luo, Yuhao; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

    2016-01-01

    Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value. PMID:27280289

  4. Local 24-h hyperglycemia does not affect endothelium-dependent or -independent vasoreactivity in humans.

    PubMed

    Houben, A J; Schaper, N C; de Haan, C H; Huvers, F C; Slaaf, D W; de Leeuw, P W; Nieuwenhuijzen Kruseman, C

    1996-06-01

    Hyperglycemia induces regional hemodynamic changes, as suggested by animal studies. These hemodynamic changes may play an initiating role in the pathogenesis of diabetic microangiopathy. The aim of the present study was to evaluate the effects of acute local hyperglycemia for 24 h on basal human forearm muscle and skin blood flow and endothelium-dependent and -independent vasoreactivity. Local hyperglycemia (approximately 15 mM) was induced by infusion of 5% glucose into the brachial artery of the nondominant arm. In control experiments, the same individual amount of glucose was infused intravenously in the dominant arm to correct for possible systemic effects of the infused glucose. Vasoreactivity of the forearm vasculature was evaluated by local infusion of acetylcholine (ACh), sodium nitroprusside (SNP), NG-monomethyl-L-arginine (L-NMMA), and norepinephrine (NE) into the brachial artery. Regional hemodynamic measurements were performed at baseline and after 6, 12, and 24 h of local hyperglycemia. Median (with interquartile range) basal forearm (muscle) blood flow (FBF) was not influenced by the 24-h local hyperglycemia [infused-to-contralateral arm FBF ratio for glucose 1.32 (1.16-1.64) vs. control 1.54 (1.34-1.69)]. Skin microcirculatory blood flow (laser Doppler flowmetry, LDF) was not influenced by the 24-h local hyperglycemia [LDF ratio for glucose 1.00 (0.62-1.56) vs control 0.80 (0.58-1.14)]. In addition, the vasoreactivity of both muscle and skin (not shown) vasculature to ACh [percent change in FBF ratio for glucose 167% (81-263) vs. control 148% (94-211)], SNP [for glucose 486% (178-586) vs. control 293% (196-454)], L-NMMA [for glucose -36% (-56 to -22) vs. control -41% (-51 to -24)], and NE [for glucose -48% (-72 to -41) vs. control -66% (-79 to -33)] was also not affected by the local hyperglycemia. Thus, in contrast to animal studies, our results suggest that a moderate-to-severe hyperglycemia does not affect the regulation of basal blood flow or

  5. IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function.

    PubMed

    Park, Jung-Bum; Nagar, Harsha; Choi, Sujeong; Jung, Saet-Byel; Kim, Hyun-Woo; Kang, Shin Kwang; Lee, Jun Wan; Lee, Jin Hyup; Park, Jeen-Woo; Irani, Kaikobad; Jeon, Byeong Hwa; Song, Hee-Jung; Kim, Cuk-Seong

    2016-05-01

    Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and cancer cells. However, the function of IDH2 in vascular endothelial cells is mostly unknown. In this study the effects of IDH2 deficiency on mitochondrial and vascular function were investigated in endothelial cells. IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial-specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown-induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function. PMID:26898144

  6. Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women.

    PubMed

    Ceresini, Graziano; Marchini, Lorenzo; Rebecchi, Isabella; Morganti, Simonetta; Bertone, Luca; Montanari, Ilaria; Bacchi-Modena, Alberto; Sgarabotto, Maria; Baldini, Monica; Denti, Licia; Ablondi, Fabrizio; Ceda, Gian Paolo; Valenti, Giorgio

    2003-03-01

    Raloxifene is one of the most important selective estrogen receptor modulators currently employed for the treatment of postmenopausal osteoporosis. However, it has also been suggested that this compound affects the vascular system. We evaluated both carotid blood flow resistance and endothelium-dependent vasodilation in 50 healthy postmenopausal women randomly assigned to receive, in a double blind design, either raloxifene (60 mg per day; N=25 subjects) or placebo (N=25 subjects) for 4 months. Indices of carotid blood flow resistance, such as the pulsatility index (PI) and resistance index (RI), as well as the flow-mediated brachial artery dilation were measured both at baseline and at the end of treatment. Changes in PI were -1.86+/-2.24 and -2.15+/-2.22% after placebo and raloxifene treatment, respectively, with no significant differences between groups. Changes in RI were -0.77+/-1.72 and -1.81+/-1.54% after placebo and raloxifene treatment, respectively, with no significant differences between groups. At the end of the treatment period, the increments in artery diameter measured after the flow stimulus were 10.79+/-2.39 and 6.70+/-1.23% for placebo and raloxifene, respectively, with no significant differences between groups. These results demonstrate no significant effects of raloxifene on either carotid blood flow resistance or brachial artery flow-mediated dilation in postmenopausal women. PMID:12618276

  7. Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway

    PubMed Central

    2010-01-01

    Introduction Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite. Methods Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clearance measurement. Arcuate renal arteries were isolated for vasoreactivity experiment and kidneys snap frozen for staining. Results High tidal volume ventilation resulted in lung injury, hypotension, renal hypoperfusion and impaired renal endothelium-dependent vasodilation, associated with renal dysfunction and tissue changes (leukocyte accumulation and increased expression of neutrophil gelatinase-associated lipocalin). Both WW85 and PJ-34 treatments attenuated lung injury, preserved blood pressure, attenuated renal endothelial dysfunction and maintained renal blood flow. In multivariable analysis, renal blood flow improvement was, independently from each other, associated with both maintained blood pressure

  8. Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O2 dependent?

    PubMed Central

    Marshall, Janice M; Ray, Clare J

    2012-01-01

    This review considers the contributions to exercise hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis. PMID:23045341

  9. Blood pressure lowering effect of the extract of aerial parts of Capparis aphylla is mediated through endothelium-dependent and independent mechanisms.

    PubMed

    Shah, Abdul Jabbar; Gilani, Anwarul Hassan

    2011-01-01

    This investigation was aimed to provide pharmacological evidences for the medicinal use of Capparis aphylla in hypertension. In normotensive anesthetized rats, intravenous administration of the crude extract of Capparis aphylla (Ca.Cr; 3-100 mg/kg) caused a fall in mean arterial pressure (MAP), which was partially blocked in the presence of atropine (2 mg/kg). In isolated rabbit aortic rings, Ca.Cr inhibited phenylephrine (1 μM) and high K(+) (80 mM) precontractions with respective EC(50) values of 0.10 (0.07-0.15) and 1.22 mg/mL (1.00-1.50), suggesting calcium channel blocking (CCB) activity with a predominant inhibitory effect on receptor operated Ca(2+) channels. Pretreatment of the arotic rings with Ca.Cr (0.1-1 mg/mL) caused a rightward shift in the Ca(2+) concentration response curves, similar to verapamil. In isolated rat aorta preparations, Ca.Cr caused a partial endothelium-dependent L-NAME/atropine-sensitive vasodilator effect. In guinea-pig atria, Ca.Cr suppressed both rate and force of spontaneous atrial contractions with respective EC(50) values of 1.35 (1.01-1.79) and 1.60 mg/mL (1.18-2.17), which remained unchanged in the presence of atropine (1 μM). These data indicate that the blood pressure (BP) lowering effect of the crude extract of Capparis aphylla is mediated through a vasodilator and cardiac depressant effect. The vasodilator effect is partly mediated by an endothelium-dependent, atropine-sensitive NO pathway, while the CCB effect is partly responsible for endothelium-independent vasodilatation and also for the cardiac depressant effect; thus, this study provides pharmacologic evidence with respect to the medicinal use of the plant in hypertension. PMID:21978026

  10. Characteristics of arterial wall shear stress which cause endothelium-dependent vasodilatation in the anaesthetized dog

    PubMed Central

    Snow, H M; Markos, F; O'Regan, D; Pollock, K

    2001-01-01

    The effects of changes in the mean and amplitude of arterial wall shear stress on endothelium-dependent arterial dilatation of the iliac artery of the anaesthetized dog were examined. Changes in the mean and amplitude of blood flow and wall shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and the stimulation of the left ansa subclavia. Changes in the diameter of a segment of the iliac artery with the endothelium intact, relative to a segment with no endothelium, were used as an index of the release of nitric oxide. The increase in mean blood flow was from 84 ± 12 to 527 ± 53 ml min−1 and in amplitude was from 365 ± 18 to 695 ± 38 ml min−1 (means ±s.e.m.). The increase in mean wall shear stress was from 1.78 ± 0.30 to 7.66 ± 1.01 N m−2 and in amplitude was from 7.37 ± 0.46 to 13.9 ± 2.00 N m−2 (means ±s.e.m.). Increases in mean shear stress caused an increase in the diameter only of the section of artery with endothelium; the slope of the relationship was 0.064 ± 0.006 mm N−1 m2 (mean ±s.e.m., P < 0.001); changes in the amplitude of shear stress did not cause an increase in diameter. Changes in both the mean and amplitude of shear stress had no significant effect on the diameter of the section of artery with no endothelium. These findings coupled with the known anti-atheroma effects of nitric oxide and the effect of shear stress on cell adhesion and platelet aggregation offer a possible explanation for the disposition of atheroma in those parts of the arterial system which have low mean and high amplitude of wall shear stress. PMID:11251063

  11. Acyl chain-dependent effect of lysophosphatidylcholine on endothelium-dependent vasorelaxation.

    PubMed

    Rao, Shailaja P; Riederer, Monika; Lechleitner, Margarete; Hermansson, Martin; Desoye, Gernot; Hallström, Seth; Graier, Wolfgang F; Frank, Saša

    2013-01-01

    Previously we identified palmitoyl-, oleoyl-, linoleoyl-, and arachidonoyl-lysophosphatidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the impact of those LPC on acetylcholine (ACh)- induced vascular relaxation. All tested LPC attenuated ACh-induced relaxation, measured ex vivo, using mouse aortic rings and wire myography. The rank order of potency was as follows: 18:2>20:4>16:0>18:1. The attenuating effect of LPC 16:0 on relaxation was augmented by indomethacin-mediated cyclooxygenase (COX)-inhibition and CAY10441, a prostacyclin (PGI2)- receptor (IP) antagonist. Relaxation attenuated by LPC 20:4 and 18:2 was improved by indomethacin and SQ29548, a thromboxane A2 (TXA2)- receptor antagonist. The effect of LPC 20:4 could also be improved by TXA2- and PGI2-synthase inhibitors. As determined by EIA assays, the tested LPC promoted secretion of PGI2, TXA2, PGF2α, and PGE2, however, with markedly different potencies. LPC 16:0 was the most potent inducer of superoxide anion production by mouse aortic rings, followed by LPC 18:2, 20:4 and 18:1, respectively. The strong antioxidant tempol recovered relaxation impairment caused by LPC 18:2, 18:1 and 20:4, but not by LPC 16:0. The tested LPC attenuate ACh-induced relaxation through induction of proconstricting prostanoids and superoxide anions. The potency of attenuating relaxation and the relative contribution of underlying mechanisms are strongly related to LPC acyl-chain length and degree of saturation. PMID:23741477

  12. Daily Relaxation Response Breaks in a Working Population

    PubMed Central

    Peters, Ruanne K.; Benson, Herbert; Porter, Douglas

    1977-01-01

    An experiment conducted at the corporate offices of a manufacturing firm investigated the effects of daily relaxation breaks on five self-reported measures of health, performance, and well-being. For 12 weeks, 126 volunteers filled out daily records and reported bi-weekly for additional measurements. After four weeks of baseline monitoring, they were divided randomly into three groups: Group A was taught a technique for producing the relaxation response; Group B was instructed to sit quiety; Group C received no instructions. Groups A and B were asked to take two 15-minute relaxation breaks daily. After an eight-week experimental period, the greatest mean improvements on every index occurred in Group A; the least improvements occurred in Group C; Group B was intermediate. Differences between the mean changes in Groups A vs C reached statistical significance (p < 0.05) on four of the five indices: Symptoms, Illness Days, Performance, and Sociability-Satisfaction. Improvements on the Happiness-Unhappiness Index were not significantly different among the three groups. The relationship between amount of change and rate of practicing the relaxation response was different for the different indices. While less than three practice periods per week produced little change on any index, two daily sessions appeared to be more practice than was necessary for many individuals to achieve positive changes. Somatic symptoms and performance responded with less practice of the relaxation response than did behavioral symptoms and measures of well-being. (Am. J. Public Health 67:946-953,1977) PMID:333957

  13. Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae.

    PubMed

    Howitt, Lauren; Grayson, T Hilton; Morris, Margaret J; Sandow, Shaun L; Murphy, Timothy V

    2012-06-15

    Obesity is a risk factor for hypertension and other vascular disease. The aim of this study was to examine the effect of diet-induced obesity on endothelium-dependent dilation of rat cremaster muscle arterioles. Male Sprague-Dawley rats (213 ± 1 g) were fed a cafeteria-style high-fat or control diet for 16-20 wk. Control rats weighed 558 ± 7 g compared with obese rats 762 ± 12 g (n = 52-56; P < 0.05). Diet-induced obesity had no effect on acetylcholine (ACh)-induced dilation of isolated, pressurized (70 mmHg) arterioles, but sodium nitroprusside (SNP)-induced vasodilation was enhanced. ACh-induced dilation of arterioles from control rats was abolished by a combination of the K(Ca) blockers apamin, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), and iberiotoxin (IBTX; all 0.1 μmol/l), with no apparent role for nitric oxide (NO). In arterioles from obese rats, however, IBTX had no effect on responses to ACh while the NO synthase (NOS)/guanylate cyclase inhibitors N(ω)-nitro-L-arginine methyl ester (L-NAME; 100 μmol/l)/1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μmol/l) partially inhibited ACh-induced dilation. Furthermore, NOS activity (but not endothelial NOS expression) was increased in arteries from obese rats. L-NAME/ODQ alone or removal of the endothelium constricted arterioles from obese but not control rats. Expression of caveolin-1 and -2 oligomers (but not monomers or caveolin-3) was increased in arterioles from obese rats. The number of caveolae was reduced in the endothelium of arteries, and caveolae density was increased at the ends of smooth muscle cells from obese rats. Diet-induced obesity abolished the contribution of large-conductance Ca(2+)-activated K(+) channel to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles, while increasing NOS activity and inducing an NO-dependent component. PMID:22492718

  14. Vascular microRNA-204 is remotely governed by the microbiome and impairs endothelium-dependent vasorelaxation by downregulating Sirtuin1.

    PubMed

    Vikram, Ajit; Kim, Young-Rae; Kumar, Santosh; Li, Qiuxia; Kassan, Modar; Jacobs, Julia S; Irani, Kaikobad

    2016-01-01

    Gut microbiota promotes atherosclerosis, and vascular endothelial dysfunction, signalled by impaired endothelium-dependent vasorelaxation, is an early marker of atherosclerosis. Here we show that vascular microRNA-204 (miR-204) expression is remotely regulated by the microbiome, and impairs endothelial function by targeting the Sirtuin1 lysine deacetylase (Sirt1). MiR-204 is downregulated, while Sirt1 is upregulated, in aortas of germ-free mice. Suppression of gut microbiome with broad-spectrum antibiotics decreases miR-204, increases Sirt1 and bioavailable vascular nitric oxide, and improves endothelium-dependent vasorelaxation in mouse aortas. Antibiotics curtail aortic miR-204 upregulation, and rescue decline of aortic Sirt1 and endothelium-dependent vasorelaxation, triggered by high-fat diet feeding. Improvement of endothelium-dependent vasorelaxation by antibiotics is lost in mice lacking endothelial Sirt1. Systemic antagonism of miR-204 rescues impaired endothelium-dependent vasorelaxation and vascular Sirt1, and decreases vascular inflammation induced by high-fat diet. These findings reveal a gut microbe-vascular microRNA-Sirtuin1 nexus that leads to endothelial dysfunction. PMID:27586459

  15. Structural relaxation and rheological response of a driven amorphous system.

    PubMed

    Varnik, F

    2006-10-28

    The interplay between the structural relaxation and the rheological response of a simple amorphous system {a 80:20 binary Lennard-Jones mixture [W. Kob and H. C. Andersen, Phys. Rev. Lett. 73, 1376 (1994)]} is studied via molecular dynamics simulations. In the quiescent state, the model is well known for its sluggish dynamics and a two step relaxation of correlation functions at low temperatures. An ideal glass transition temperature of Tc=0.435 has been identified in the previous studies via the analysis of the system's dynamics in the framework of the mode coupling theory of the glass transition [W. Kob and H. C. Andersen, Phys. Rev. E 51, 4626 (1995)]. In the present work, we focus on the question whether a signature of this ideal glass transition can also be found in the case where the system's dynamics is driven by a shear motion. Indeed, the following distinction in the structural relaxation is found: In the supercooled state, the structural relaxation is dominated by the shear at relatively high shear rates gamma, whereas at sufficiently low gamma the (shear-independent) equilibrium relaxation is recovered. In contrast to this, the structural relaxation of a glass is always driven by shear. This distinct behavior of the correlation functions is also reflected in the rheological response. In the supercooled state, the shear viscosity eta decreases with increasing shear rate (shear thinning) at high shear rates, but then converges toward a constant as the gamma is decreased below a (temperature-dependent) threshold value. Below Tc, on the other hand, the shear viscosity grows as eta proportional, etax 1/gamma, suggesting a divergence at gamma=0. Thus, within the accessible observation time window, a transition toward a nonergodic state seems to occur in the driven glass as the driving force approaches zero. As to the flow curves (stress versus shear rate), a plateau forms at low shear rates in the glassy phase. A consequence of this stress plateau for

  16. Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels.

    PubMed Central

    Kamata, K.; Mori, T.; Shigenobu, K.; Kasuya, Y.

    1989-01-01

    1. To elucidate the mechanisms of the powerful and long-lasting hypotension produced by platelet activating factor (PAF), its effects on perfusion pressure in the perfused mesenteric arterial bed of the rat were examined. 2. Infusion of PAF (10(-11) to 3 x 10(-10) M; EC50 = 4.0 x 10(-11) M; 95%CL = 1.6 x 10(-11) - 9.4 x 10(-11) M) and acetylcholine (ACh) (10(-10) to 10(-6) M; EC50 = 3.0 +/- 0.1 x 10(-9) M) produced marked concentration-dependent vasodilatations which were significantly inhibited by treatment with detergents (0.1% Triton X-100 for 30 s or 0.3% CHAPS for 90 s). 3. Pretreatment with CV-6209, a PAF antagonist, inhibited PAF- but not ACh-induced vasodilation. 4. Treatment with indomethacin (10(-6) M) had no effect on PAF- or ACh-induced vasodilatation. 5. These results demonstrate that extremely low concentrations of PAF produce vasodilatation of resistance vessels through the release of endothelium-derived relaxing factor (EDRF). This may account for the strong hypotension produced by PAF in vivo. PMID:2611496

  17. Apamin-sensitive K+ channels mediate an endothelium-dependent hyperpolarization in rabbit mesenteric arteries.

    PubMed Central

    Murphy, M E; Brayden, J E

    1995-01-01

    1. Vascular endothelial cells release a variety of substances which affect the membrane potential and tone of underlying vascular smooth muscle. In the presence of N omega-nitro-L-arginine to inhibit nitric oxide synthase and indomethacin to inhibit cyclo-oxygenase, acetylcholine (ACh; EC50 approximately 1 microM) elicited the release of an endothelium-derived hyperpolarizing factor (EDHF) in rabbit mesenteric arteries. 2. The hyperpolarization due to EDHF was blocked by apamin (IC50 approximately 0.3 nM), and by other inhibitors of the apamin-sensitive K+ channel (10 nM scyllatoxin, 100 microM d-tubocurarine, 300 microM gallamine) in the presence of indomethacin and N omega-nitro-L-arginine. The hyperpolarization was not blocked by glibenclamide (5 microM), iberiotoxin (10 nM), tetraethylammonium (1 mM), barium (500 microM), 4-aminopyridine (500 microM), ouabain (10 microM), bumetanide (10 microM), or nimodipine (100 nM). 3. In the presence of apamin and N omega-nitro-L-arginine, but the absence of indomethacin, ACh triggered a hyperpolarization that was blocked by glibenclamide, an inhibitor of ATP-sensitive K+ (KATP) channels. A similar glibenclamide-sensitive hyperpolarization was caused by Iloprost, a stable analogue of prostacyclin. 4. In experiments which distinguished the effects of EDHF, prostanoids and nitric oxide, hyperpolarizations and/or relaxations triggered by ACh were antagonized by muscarinic antagonists, the relative potencies (atropine approximately 4-DAMP > pirenzepine) of which indicated that the release of all three endothelium-derived factors was mediated by M3 receptors. 5. Our results suggest that ACh stimulates M3 receptors on endothelial cells, triggering the release of nitric oxide and prostanoids, which hyperpolarize underlying smooth muscle by activation of KATP channels, and the release of an EDHF, which hyperpolarizes smooth muscle through the activation of apamin-sensitive K+ (KAS) channels. Images Figure 4 PMID:8788937

  18. Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow.

    PubMed

    Kraemer-Aguiar, Luiz G; de Miranda, Marcos L; Bottino, Daniel A; Lima, Ronald de A; de Souza, Maria das Graças C; Balarini, Michelle de Moura; Villela, Nivaldo R; Bouskela, Eliete

    2015-01-01

    Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow. PMID:26913005

  19. NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries

    PubMed Central

    Trott, Daniel W.; Seawright, John W.; Luttrell, Meredith J.

    2011-01-01

    We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O2−) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H2O2), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H2O2 scavenger altered flow-induced dilation, whereas both H2O2 scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H2O2 and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA. PMID:21233343

  20. NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries.

    PubMed

    Trott, Daniel W; Seawright, John W; Luttrell, Meredith J; Woodman, Christopher R

    2011-05-01

    We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O(2)(-)) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H(2)O(2)), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H(2)O(2) scavenger altered flow-induced dilation, whereas both H(2)O(2) scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H(2)O(2) and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA. PMID:21233343

  1. EDHF, NO and a prostanoid: hyperpolarization-dependent and -independent relaxation in guinea-pig arteries

    PubMed Central

    Tare, Marianne; Parkington, Helena C; Coleman, H A

    2000-01-01

    The contribution of endothelium-derived hyperpolarizing factor (EDHF), nitric oxide (NO) and a prostanoid (PG) to endothelium-dependent hyperpolarization and relaxation were assessed in coronary and mammary arteries of guinea-pigs by integration of the responses evoked during discrete applications of acetylcholine (ACh). The results of this integration approach were compared with those using traditional peak analysis methods.Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM) and indomethacin (1 μM), alone or in combination, were without effect on peak hyperpolarizations or relaxations while they markedly reduced the integrated responses in both arteries.Integrated responses attributed to NO and PG were larger than those attributed to EDHF in the coronary artery (at 2 μM ACh, hyperpolarization (mV s): NO, 4200±91; PG, 5046±157; EDHF, 1532±94; relaxation (mN s mm−1): NO, 2488±122; PG, 2234±96; EDHF, 802±54). Integrated responses attributed to NO, PG and EDHF were similar in the mammary artery (at 2 μM ACh, hyperpolarization: NO, 347±69; PG, 217±49; EDHF, 310±63; relaxation: NO, 462±94; PG, 456±144; EDHF, 458±40).Gilbenclamide (1 μM) all but abolished the hyperpolarization attributable to NO and PG but not EDHF in both arteries allowing assessment of the role of the hyperpolarization in relaxation. Gilbenclamide was without effect on the integrated relaxation due to NO but significantly reduced the relaxation associated with PG in the two arteries.In conclusion, integration of the responses enabled a more complete assessment of the contribution of EDHF, NO and PG to endothelium-dependent responses, which were strikingly different in the two arteries. There is commonality in the role of hyperpolarization in relaxation in both arteries: EDHF-dependent relaxation is strongly dependent on hyperpolarization; hyperpolarization plays an important role in PG relaxation, whereas it has a small facilitatory role in NO-dependent relaxation. PMID

  2. Homocysteine-induced attenuation of vascular endothelium-dependent hyperalgesia in the rat.

    PubMed

    Joseph, E K; Green, P G; Ferrari, L F; Levine, J D

    2015-01-22

    We have recently demonstrated a role of the vascular endothelium in peripheral pain mechanism by disrupting endothelial cell function using intravascular administration of octoxynol-9, a non-selective membrane active agent. As an independent test of the role of endothelial cells in pain mechanisms, we evaluated the effect of homocysteine, an agent that damages endothelial cell function. Mechanical stimulus-induced enhancement of endothelin-1 hyperalgesia in the gastrocnemius muscle of the rat was first prevented then enhanced by intravenous administration of homocysteine, but was only inhibited by its precursor, methionine. Both homocysteine and methionine significantly attenuated mechanical hyperalgesia in two models of ergonomic muscle pain, induced by exposure to vibration, and by eccentric exercise, and cutaneous mechanical hyperalgesia in an ischemia-reperfusion injury model of Complex Regional Pain Syndrome type I, all previously shown responsive to octoxynol-9. This study provides independent support for a role of the endothelial cell in pain syndromes thought to have a vascular basis, and suggests that substances that are endothelial cell toxins can enhance vascular pain. PMID:25451284

  3. Unitary TRPV3 channel Ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles.

    PubMed

    Pires, Paulo W; Sullivan, Michelle N; Pritchard, Harry A T; Robinson, Jennifer J; Earley, Scott

    2015-12-15

    Cerebral parenchymal arterioles (PA) regulate blood flow between pial arteries on the surface of the brain and the deeper microcirculation. Regulation of PA contractility differs from that of pial arteries and is not completely understood. Here, we investigated the hypothesis that the Ca(2+) permeable vanilloid transient receptor potential (TRPV) channel TRPV3 can mediate endothelium-dependent dilation of cerebral PA. Using total internal reflection fluorescence microscopy (TIRFM), we found that carvacrol, a monoterpenoid compound derived from oregano, increased the frequency of unitary Ca(2+) influx events through TRPV3 channels (TRPV3 sparklets) in endothelial cells from pial arteries and PAs. Carvacrol-induced TRPV3 sparklets were inhibited by the selective TRPV3 blocker isopentenyl pyrophosphate (IPP). TRPV3 sparklets have a greater unitary amplitude (ΔF/F0 = 0.20) than previously characterized TRPV4 (ΔF/F0 = 0.06) or TRPA1 (ΔF/F0 = 0.13) sparklets, suggesting that TRPV3-mediated Ca(2+) influx could have a robust influence on cerebrovascular tone. In pressure myography experiments, carvacrol caused dilation of cerebral PA that was blocked by IPP. Carvacrol-induced dilation was nearly abolished by removal of the endothelium and block of intermediate (IK) and small-conductance Ca(2+)-activated K(+) (SK) channels. Together, these data suggest that TRPV3 sparklets cause dilation of cerebral parenchymal arterioles by activating IK and SK channels in the endothelium. PMID:26453324

  4. Effects of red and white wine on endothelium-dependent vasorelaxation of rat aorta and human coronary arteries.

    PubMed

    Flesch, M; Schwarz, A; Böhm, M

    1998-10-01

    Beneficial effects of wine on myocardial infarction mortality may be because of its vasodilatory properties. This study investigated whether the vasodilatory activity involves the endothelium and is specific for certain wines. Effects of different red and white wines and phenolic grape ingredients on vascular tension and cGMP content were studied in human coronary arteries and rat aortic rings in vitro. Only French and Italian red wines produced "en barrique" (Bordeaux, Châteauneuf du Pape, Barolo) (1:1,000, vol/vol), quercetin (1-100 microM), and tannic acid (1-100 microgram/ml) decreased tension of precontracted vascular rings and increased vascular cGMP content (both P < 0.001). The effects were abolished after endothelial denudation and reversible by nitric oxide synthase inhibition. Red wines not produced en barrique (Valpolicella, Ahr Spätburgunder), white wines (en barrique-produced Rioja, Chardonnay, Mosel-Riesling), and ethanol did not affect vascular tension or cGMP content. Thus endothelium-dependent vasodilatory effects appear to be specific for red barrique wines, possibly because of their high content of phenolic substances. Divergent effects of wines indicate that a general view on the effects of wine and alcoholic beverages is not warranted. PMID:9746465

  5. Endothelial Small- and Intermediate-Conductance K Channels and Endothelium-Dependent Hyperpolarization as Drug Targets in Cardiovascular Disease.

    PubMed

    Köhler, R; Oliván-Viguera, A; Wulff, H

    2016-01-01

    Endothelial calcium/calmodulin-gated K channels of small (KCa2.3) and intermediate conductance (KCa3.1) produce membrane hyperpolarization and endothelium-dependent hyperpolarization (EDH)-mediated vasodilation. Dysfunctions of the two channels and ensuing EDH impairments are found in several cardiovascular pathologies such as diabetes, atherosclerosis, postangioplastic neointima formation, but also inflammatory disease, cancer, and organ fibrosis. Moreover, KCa3.1 plays an important role in endothelial barrier dysfunction, edema formation in cardiac and pulmonary disease, and in ischemic stroke. Concerning KCa2.3, genome-wide association studies revealed an association of KCa2.3 channels with atrial fibrillation in humans. Accordingly, both channels are considered potential drug targets for cardio- and cerebrovascular disease states. In this chapter, we briefly review the function of the two channels in EDH-type vasodilation and systemic circulatory regulation and then highlight their pathophysiological roles in ischemic stroke as well as in pulmonary and brain edema. Finally, the authors summarize recent advances in the pharmacology of the channels and explore potential therapeutic utilities of novel channel modulators. PMID:27451095

  6. Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity.

    PubMed

    Ryan, M; McInerney, D; Owens, D; Collins, P; Johnson, A; Tomkin, G H

    2000-02-01

    Abnormalities in endothelial function may be associated with increased cardiovascular risk in diabetic patients. We examined the effect of an oleic-acid-rich diet on insulin resistance and endothelium-dependent vasoreactivity in type 2 diabetes. Eleven type 2 diabetic patients were changed from their usual linoleic-acid-rich diet and treated for 2 months with an oleic-acid-rich diet. Insulin-mediated glucose transport was measured in isolated adipocytes. Fatty acid composition of the adipocyte membranes was determined by gas-liquid chromatography and flow-mediated endothelium-dependent and -independent vasodilatation were measured in the superficial femoral artery at the end of each dietary period. There was a significant increase in oleic acid and a decrease in linoleic acid on the oleic-acid-rich diet (p<0.0001). Diabetic control was not different between the diets, but there was a small but significant decrease in fasting glucose/insulin on the oleic-acid-rich diet. Insulin-stimulated (1 ng/ml) glucose transport was significantly greater on the oleic- acid-rich diet (0.56+/-0.17 vs. 0.29+/-0.14 nmol/10(5) cells/3 min, p<0.0001). Endothelium-dependent flow-mediated vasodilatation (FMD) was significantly greater on the oleic-acid-rich diet (3.90+/-0.97% vs. 6.12+/-1.36% p<0.0001). There was a significant correlation between adipocyte membrane oleic/linoleic acid and insulin-mediated glucose transport (p<0.001) but no relationship between insulin-stimulated glucose transport and change in endothelium-dependent FMD. There was a significant positive correlation between adipocyte membrane oleic/linoleic acid and endothelium-dependent FMD (r=0.61, p<0.001). Change from polyunsaturated to monounsaturated diet in type 2 diabetes reduced insulin resistance and restored endothelium-dependent vasodilatation, suggesting an explanation for the anti-atherogenic benefits of a Mediterranean-type diet. PMID:10700478

  7. Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic aorta.

    PubMed Central

    Moritoki, H.; Hisayama, T.; Takeuchi, S.; Miyano, H.; Kondoh, W.

    1992-01-01

    1. The mechanism of the vasorelaxant effect of platelet activating factor (PAF) on rat thoracic aorta and the effect of aging on the PAF-induced relaxation were investigated. 2. PAF at concentrations causing relaxation induced marked increases in guanosine 3':5'-cyclic monophosphate (cyclic GMP) production, but did not induce an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP). 3. Removal of the endothelium by mechanical rubbing, and treatment with the PAF antagonists CV-3988, CV-6209 and FR-900452, the nitric oxide biosynthesis inhibitor, NG-nitro L-arginine, the radical scavenger, haemoglobin, and the soluble guanylate cyclase inhibitor, methylene blue, inhibited PAF-induced relaxation and abolished or attenuated PAF-stimulated cyclic GMP production. 4. The relaxation was greatest in arteries from rats aged 4 weeks. With an increase in age, the response of the arteries to PAF was attenuated. 5. Endothelium-dependent cyclic GMP production also decreased with increase in age of the rats. 6. These results suggest that PAF stimulates production of nitric oxide from L-arginine by acting on the PAF receptors in the endothelium, which in turn stimulates soluble guanylate cyclase in the smooth muscle cells, and so increases production of cyclic GMP, thus relaxing the arteries. Age-associated decrease in PAF-induced relaxation may result from a reduction of cyclic GMP formation. PMID:1358382

  8. Time to Relax: Mechanical Stress Release Guides Stem Cell Responses.

    PubMed

    Sommerfeld, Sven D; Elisseeff, Jennifer H

    2016-02-01

    Stem cells integrate spatiotemporal cues, including the mechanical properties of their microenvironment, into their fate decisions. Chaudhuri et al. (2015) show that the ability of the extracellular matrix to dissipate cell-induced forces, referred to as stress-relaxation, is a key mechanical signal influencing stem cell fate and function. PMID:26849301

  9. Characterization of the relaxant response to taurine in rat corpus cavernosum.

    PubMed

    Dalaklioglu-Tasatargil, S

    2013-01-01

    The aim of this study was to evaluate the relaxant effect of taurine, one of the most commonly employed dietary supplements, in rat corpus cavernosum (CC), and to further investigate the contribution of possible underlying mechanisms. Strips of CC were suspended in an organ bath system for isometric tension studies. Taurine (10-80 mmol/l) produced a concentration-dependent relaxation response in rat CC. Endothelial removal did not cause a significant inhibition of the relaxation response to taurine. Incubation of endothelium-denuded CC strips with the nonselective potassium channel blocker tetraethylammonium (10 mmol/l), the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 μmol/l), the inward rectifier potassium (Kir) channel inhibitor barium chloride (30 μmol/l), and the large conductance calcium-activated potassium channel inhibitor iberiotoxin (0.1 μmol/l) significantly inhibited the relaxant responses to taurine. However, taurine-induced relaxation was not inhibited by the voltage-dependent potassium channel inhibitor 4-aminopyridine (1 mmol/l). On the other hand, taurine (20 mmol/l, 30 min) inhibited both intracellular and extracellular calcium-dependent contraction in CC strips. These findings suggest that taurine induced relaxation of CC via an endothelium-independent pathway. The activation of KATP channels, Kir channels and calcium channels is thought to play an important role in endothelium-independent relaxation of CC, but other direct effects on calcium dynamics may also contribute to its relaxant effect. PMID:23615068

  10. Identification of Structural Relaxation in the Dielectric Response of Water

    NASA Astrophysics Data System (ADS)

    Hansen, Jesper S.; Kisliuk, Alexander; Sokolov, Alexei P.; Gainaru, Catalin

    2016-06-01

    One century ago pioneering dielectric results obtained for water and n -alcohols triggered the advent of molecular rotation diffusion theory considered by Debye to describe the primary dielectric absorption in these liquids. Comparing dielectric, viscoelastic, and light scattering results, we unambiguously demonstrate that the structural relaxation appears only as a high-frequency shoulder in the dielectric spectra of water. In contrast, the main dielectric peak is related to a supramolecular structure, analogous to the Debye-like peak observed in monoalcohols.

  11. Identification of Structural Relaxation in the Dielectric Response of Water.

    PubMed

    Hansen, Jesper S; Kisliuk, Alexander; Sokolov, Alexei P; Gainaru, Catalin

    2016-06-10

    One century ago pioneering dielectric results obtained for water and n-alcohols triggered the advent of molecular rotation diffusion theory considered by Debye to describe the primary dielectric absorption in these liquids. Comparing dielectric, viscoelastic, and light scattering results, we unambiguously demonstrate that the structural relaxation appears only as a high-frequency shoulder in the dielectric spectra of water. In contrast, the main dielectric peak is related to a supramolecular structure, analogous to the Debye-like peak observed in monoalcohols. PMID:27341258

  12. Atomistic modeling of electron relaxation effect on femtosecond laser-induced thermoelastic response of gold films

    NASA Astrophysics Data System (ADS)

    Xiong, Q. L.; Tian, X. G.; Lu, T. J.

    2012-07-01

    The thermoelastic response of thin gold films induced by femtosecond laser irradiation is numerically simulated using a modified combined two-temperature model (TTM) and molecular dynamics (MD) method, with focus placed upon the influence of the electron relaxation effect. The validity of the numerical approach is checked against existing experimental results. While the electron relaxation effect is found negligible when the laser duration is much longer than the electron thermal relaxation time, it becomes significant if the laser duration matches the electron relaxation time, especially when the former is much shorter than the latter. The characteristics of thermo-mechanical interaction in the thin film are analyzed, and the influence of temperature-dependent material properties upon the thermoelastic response of the film quantified.

  13. Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway.

    PubMed

    Xia, Tianyang; Guan, Weiwei; Fu, Jinjuan; Zou, Xue; Han, Yu; Chen, Caiyu; Zhou, Lin; Zeng, Chunyu; Wang, Wei Eric

    2016-06-01

    Tirofiban, a glycoprotein IIb/IIIa inhibitor, is an antiplatelet drug extensively used in patients with acute coronary syndrome (ACS) and exerts an therapeutic effect on no-reflow phenomenon during percutaneous coronary intervention (PCI). Previous studies elucidated the vasodilation caused by tirofiban in the peripheral artery. However, whether tirofiban exerts a vasodilator effect on the coronary artery is unclear. Our present study found that tirofiban induced endothelium-dependent vasodilation in a concentration- and time-dependent manner in the isolated rat coronary artery pre-constricted by 5-hydroxytryptamine (5-HT). Further study showed that incubation of human umbilical venous endothelial cells (HUVECs) with tirofiban increased NO production, which was ascribed to the increased eNOS phosphorylation. This was confirmed by the loss of the vasorelaxant effect of tirofiban in the presence of l-NAME (eNOS inhibitor) and L-NMMA (NOS inhibitor) but not SMT (iNOS inhibitor) on isolated rat coronary arteries. The vasorelaxation was also blocked by the PI3K inhibitors, wortmannin and LY294002, as well as the Akt inhibitor SH-5, indicating the role of PI3K and Akt in tirofiban-mediated vasodilation. Moreover, further study showed that soluble guanylyl cyclase (sGC) inhibitor ODQ, or blockers of potassium channel (big-conductance calcium-activated potassium channel) blocked tirofiban-induced vasodilation of the coronary artery. These findings suggest that tirofiban induces vasorelaxation via an endothelium-dependent NO-cGMP signaling through the activation of the Akt/eNOS/sGC pathway. PMID:27018249

  14. The expression of p66shc in peripheral blood monocytes is increased in patients with coronary heart disease and correlated with endothelium-dependent vasodilatation.

    PubMed

    Miao, Qin; Wang, Qiong; Dong, Lini; Wang, Yanjiao; Tan, Yi; Zhang, Xiangyu

    2015-07-01

    The objective of this study is to detect the p66shc mRNA and protein expression of the peripheral blood monocytes (PBMs) in coronary heart disease patients (CHD) and controls, to evaluate the correlation between the expression of p66shc mRNA in the PBMs and endothelium-dependent vasodilatation. This study included 78 coronary angiography-documented CHD patients (CHD group) and 38 non-CHD controls (control group). The p66shc mRNA and protein levels were determined by quantitative real-time PCR and western blotting. The flow-mediated dilatation (FMD, endothelium-dependent), nitroglycerine-induced dilatation (NID, endothelium-independent) and carotid intimal medial thickness (CIMT) were detected using high-resolution ultrasound. The p66shc mRNA and the protein expression levels in the PBMs were significantly higher in the CHD group compared with the control group (p = 0.007 and 0.001). The FMD (p < 0.001) and NID (p = 0.013) were significantly lower and the CIMT (p = 0.007) was significantly thicker in the CHD patients than in the controls. In the univariate analysis, the expression of the p66shc mRNA in the PBMs was significantly positively correlated with the serum LDL-C and homocysteine levels and the CIMT and was inversely correlated with the FMD and the NID (all p < 0.001). In the multiple linear regression analysis, the FMD (p < 0.001), LDL-C (p = 0.002) and homocysteine levels (p = 0.002) remained independently correlated with the p66shc mRNA expression. These findings highlight a pivotal role for the expression of p66shc in CHD and endothelial dysfunction, which might represent a molecular target to prevent endothelial dysfunction-related disease. PMID:24676406

  15. Dielectric relaxations and dielectric response in multiferroic BiFeO{sub 3} ceramics

    SciTech Connect

    Hunpratub, Sitchai; Thongbai, Prasit; Maensiri, Santi; Yamwong, Teerapon; Yimnirun, Rattikorn

    2009-02-09

    Single-phase multiferroic BiFeO{sub 3} ceramics were fabricated using pure precipitation-prepared BiFeO{sub 3} powder. Dielectric response of BiFeO{sub 3} ceramics was investigated over a wide range of temperature and frequency. Our results reveal that the BiFeO{sub 3} ceramic sintered at 700 deg. C exhibited high dielectric permittivity, and three dielectric relaxations were observed. A Debye-type dielectric relaxation at low temperatures (-50 to 20 deg. C) is attributed to the carrier hopping process between Fe{sup 2+} and Fe{sup 3+}. The other two dielectric relaxations at the temperature ranges 30-130 deg. C and 140-200 deg. C could be due to the grain boundary effect and the defect ordering and/or the conductivity, respectively.

  16. Integrating a relaxation response-based curriculum into a public high school in Massachusetts.

    PubMed

    Foret, Megan M; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R

    2012-04-01

    Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes in perceived stress, anxiety, self-esteem, health-promoting behaviors, and locus of control) of a relaxation response (RR)-based curriculum integrated into the school day for high school students. The curriculum included didactic instruction, relaxation exercises, positive psychology, and cognitive restructuring. The intervention group showed significantly greater improvements in levels of perceived stress, state anxiety, and health-promoting behaviors when compared to the wait list control group. The intervention appeared most useful for girls in the intervention group. The results suggest that several modifications may increase the feasibility of using this potentially effective intervention in high schools. PMID:21893336

  17. AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension

    PubMed Central

    Sonkusare, Swapnil K.; Dalsgaard, Thomas; Bonev, Adrian D.; Hill-Eubanks, David C.; Kotlikoff, Michael I.; Scott, John D.; Santana, Luis F.; Nelson, Mark T.

    2015-01-01

    Endothelial cell dysfunction, characterized by a diminished response to endothelial cell–dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vaso-dilation, a function mediated by local Ca2+ influx through clusters of functionally coupled TRPV4 channels rather than by a global increase in endothelial cell Ca2+. We showed that stimulation of muscarinic acetylcholine receptors on endothelial cells of mouse arteries exclusively activated TRPV4 channels that were localized at myoendothelial projections (MEPs), specialized regions of endothelial cells that contact smooth muscle cells. Muscarinic receptor–mediated activation of TRPV4 depended on protein kinase C (PKC) and the PKC-anchoring protein AKAP150, which was concentrated at MEPs. Cooperative opening of clustered TRPV4 channels specifically amplified Ca2+ influx at MEPs. Cooperativity of TRPV4 channels at non-MEP sites was much lower, and cooperativity at MEPs was greatly reduced by chelation of intracellular Ca2+ or AKAP150 knockout, suggesting that Ca2+ entering through adjacent channels underlies the AKAP150-dependent potentiation of TRPV4 activity. In a mouse model of angiotensin II–induced hypertension, MEP localization of AKAP150 was disrupted, muscarinic receptor stimulation did not activate TRPV4 channels, cooperativity among TRPV4 channels at MEPs was weaker, and vasodilation in response to muscarinic receptor stimulation was reduced. Thus, endothelial-dependent dilation of resistance arteries is enabled by MEP-localized AKAP150, which ensures the proximity of PKC to TRPV4 channels and the coupled channel gating necessary for efficient communication from endothelial to smooth muscle cells in arteries. Disruption of this molecular assembly may contribute to altered blood flow in hypertension. PMID:25005230

  18. Cilostazol Enhances Mobilization of Circulating Endothelial Progenitor Cells and Improves Endothelium-Dependent Function in Patients at High Risk of Cardiovascular Disease.

    PubMed

    Chao, Ting-Hsing; Chen, I-Chih; Lee, Cheng-Han; Chen, Ju-Yi; Tsai, Wei-Chuan; Li, Yi-Heng; Tseng, Shih-Ya; Tsai, Liang-Miin; Tseng, Wei-Kung

    2016-08-01

    This is the first study to investigate the vasculoangiogenic effects of cilostazol on endothelial progenitor cells (EPCs) and flow-mediated dilatation (FMD) in patients at high risk of cardiovascular disease (CVD). This double-blind, placebo-controlled study included 71 patients (37 received 200 mg/d cilostazol and 34 received placebo for 12 weeks). Use of cilostazol, but not placebo, significantly increased circulating EPC (kinase insert domain receptor(+)CD34(+)) counts (percentage changes: 149.0% [67.9%-497.8%] vs 71.9% [-31.8% to 236.5%], P = .024) and improved triglyceride and high-density lipoprotein cholesterol levels (P = .002 and P = .003, respectively). Plasma levels of vascular endothelial growth factor (VEGF)-A165 and FMD significantly increased (72.5% [32.9%-120.4%] vs -5.8% [-46.0% to 57.6%], P = .001; 232.8% ± 83.1% vs -46.9% ± 21.5%, P = .003, respectively) in cilostazol-treated patients. Changes in the plasma triglyceride levels significantly inversely correlated with the changes in the VEGF-A165 levels and FMD. Cilostazol significantly enhanced the mobilization of EPCs and improved endothelium-dependent function by modifying some metabolic and angiogenic markers in patients at high risk of CVD. PMID:27401788

  19. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

    PubMed Central

    Celotto, A.C.; Ferreira, L.G.; Capellini, V.K.; Albuquerque, A.A.S.; Rodrigues, A.J.; Evora, P.R.B.

    2015-01-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control. PMID:26648089

  20. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect.

    PubMed

    Celotto, A C; Ferreira, L G; Capellini, V K; Albuquerque, A A S; Rodrigues, A J; Evora, P R B

    2016-02-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control. PMID:26648089

  1. Highly nonlinear stress-relaxation response of articular cartilage in indentation: Importance of collagen nonlinearity.

    PubMed

    Mäkelä, J T A; Korhonen, R K

    2016-06-14

    Modern fibril-reinforced computational models of articular cartilage can include inhomogeneous tissue composition and structure, and nonlinear mechanical behavior of collagen, proteoglycans and fluid. These models can capture well experimental single step creep and stress-relaxation tests or measurements under small strains in unconfined and confined compression. Yet, it is known that in indentation, especially at high strain velocities, cartilage can express highly nonlinear response. Different fibril reinforced poroelastic and poroviscoelastic models were used to assess measured highly nonlinear stress-relaxation response of rabbit articular cartilage in indentation. Experimentally measured depth-dependent volume fractions of different tissue constituents and their mechanical nonlinearities were taken into account in the models. In particular, the collagen fibril network was modeled using eight separate models that implemented five different constitutive equations to describe the nonlinearity. These consisted of linear elastic, nonlinear viscoelastic and multiple nonlinear elastic representations. The model incorporating the most nonlinearly increasing Young׳s modulus of collagen fibrils as a function of strain captured best the experimental data. Relative difference between the model and experiment was ~3%. Surprisingly, the difference in the peak forces between the experiment and the model with viscoelastic collagen fibrils was almost 20%. Implementation of the measured volume fractions did not improve the ability of the model to capture the measured mechanical data. These results suggest that a highly nonlinear formulation for collagen fibrils is needed to replicate multi-step stress-relaxation response of rabbit articular cartilage in indentation with high strain rates. PMID:27130474

  2. A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

    PubMed Central

    2011-01-01

    Background Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. Methods and design 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Discussion Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. Trial registration NCT00872365. PMID:21356082

  3. Effect of Mesenchymal Precursor Cells on the Systemic Inflammatory Response and Endothelial Dysfunction in an Ovine Model of Collagen-Induced Arthritis

    PubMed Central

    Dooley, Laura M.; Abdalmula, Anwar; Washington, Elizabeth A.; Kaufman, Claire; Tudor, Elizabeth M.; Ghosh, Peter; Itescu, Silviu; Kimpton, Wayne G.; Bailey, Simon R.

    2015-01-01

    Background and Aim Mesenchymal precursor cells (MPC) are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model. Methods Arthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction. Results and Conclusion Arthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls), and digital arteries also demonstrated greater endothelium-dependent vasodilation

  4. A microstructural investigation of the depth-dependent response of cartilage during stress relaxation

    NASA Astrophysics Data System (ADS)

    Zhang, Geran; Thambyah, Ashvin; Broom, Neil

    2009-08-01

    The poro-visco-hyperelastic nature of articular cartilage has been studied extensively, yet little has been done to correlate its unique mechanical properties with its microstructural response to load. Making such a correlation would help determine how the microstructure of cartilage, with its zonally-differentiated fibrillar microarchitecture and water-content, influences the overall macro-level mechanical response. A total of eight cartilage-on-bone samples were subjected to stress relaxation tests, conducted via stepwise indentation, and using a 2mm diameter cylindrical indenter. Each step indentation consisted of a 10% compressive strain, up to 80%. At each strain increment the specimen was allowed to fully relax to an equilibrium stress before compressing it further. From the stress relaxation curve at each strain level, peak and equilibrium stresses were recorded. For the microstructural investigation, specimens stress-equilibrated at 20%, 40%, 60% and 80% strain, were chemically fixed to capture the deformed state and then cryo-sectioned and imaged using differential interference contrast (DIC) microscopy. It was found that stress relaxation, i.e. the time from peak stress to equilibrium, occurred at a slower rate at the larger levels of compressive strain. Peak stresses increased exponentially with increasing levels of strain. The equilibrium stress relationship with compressive strain level was largely linear but between 60% and 80% strain, the change in equilibrium stress increased dramatically. The microstructural data showed how at lower strain levels, much of the load was distributed laterally within the upper zones of the cartilage matrix. At higher strain levels (>60%) the deep zone fibrillar alignment was sheared and this may explain the abrupt rise in equilibrium stress levels. Finally, the increase in peak stress at higher strain-levels is likely due to a decreased interstitial fluid permeability associated with an increasingly consolidated matrix.

  5. Effects of physical fitness on relaxed G-tolerance and the exercise pressor response.

    PubMed

    Kölegård, Roger; Mekjavic, Igor B; Eiken, Ola

    2013-11-01

    Fighter pilots are commonly recommended strength training as a means of improving the tolerance to withstand high gravitoinertial (G) loads. Previous studies on the effect of short-term strength-training regimens on G-endurance show equivocal results, with a majority of the studies suggesting improved G-endurance. The mechanisms underlying such improvement are unknown. Presumably, any change in G-tolerance induced by physical training habits should be manifest following long-term training. We also reasoned that during repeated straining maneuvers--as during certain G-endurance protocols--the relaxed G-tolerance and the exercise pressure response may play a significant role in maintaining adequate arterial pressure, and hence that different training modalities might alter G-endurance, by altering the exercise pressor response. Three groups of males were studied, long-term (>6 months) endurance-trained (E; n = 17), strength-trained (S; n = 16) and untrained (U; n = 17) individuals. The pressor response was studied during sustained (40 s) isometric knee extensions at 50 % of the maximal contraction level. Relaxed gradual onset-rate G-tolerance was determined. G-tolerance was similar in the E (4.6 ± 0.5 G), S (4.9 ± 0.8 G) and U (4.6 ± 0.8 G) groups. The mean arterial pressure increase during isometric exercise was higher in the S (36 ± 7 mmHg = mean ± SD) and U (35 ± 16 mmHg) groups than in the E group (28 ± 8 mmHg). The results suggest that relaxed G-tolerance is unaffected by physical training habits, and that the training modality affects the magnitude of the exercise pressor response. However, it seems that the response is blunted by endurance training rather than enhanced by strength training. PMID:23989489

  6. Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery: The Role of Potassium Signaling

    PubMed Central

    Hangaard, Lise; Jessen, Peter B.; Kamaev, Dmitrii; Aalkjaer, Christian; Matchkov, Vladimir V.

    2015-01-01

    The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca2+-activated K+ channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca2+]out. Also it has been suggested that K+ is important through localized [K+]out signaling causing activation of the Na+,K+-ATPase and inward-rectifying K+ channels (Kir). Here we tested the hypothesis that the modulating effect of [Ca2+]out on the EDH-like response depends on [K+]out. We addressed this possibility using isometric myography of rat mesenteric small arteries. When [K+]out was 4.2 mM, relaxation to acetylcholine (ACh) was stronger at 2.5 mM [Ca2+]out than at 1 mM [Ca2+]out. Inhibition of IKCa with TRAM34 suppressed the relaxations but did not change the relation between the relaxations at the low and high [Ca2+]out. This [Ca2+]out-dependence disappeared at 5.9 mM [K+]out and in the presence of ouabain or BaCl2. Our results suggest that IKCa are involved in the localized [K+]out signaling which acts through the Na+,K+-ATPase and Kir channels and that the significance of this endothelium-dependent pathway is modulated by [Ca2+]out. PMID:26504829

  7. Effect of organo-clay on the dielectric relaxation response of silicone rubber

    NASA Astrophysics Data System (ADS)

    Gharavi, N.; Razzaghi-Kashani, M.; Golshan-Ebrahimi, N.

    2010-02-01

    Dielectric elastomers are light weight, low-cost, highly deformable and fast response smart materials capable of converting electrical energy into mechanical work or vice versa. Silicone rubber is a well-known dielectric elastomer which is used as actuator, and in order to enhance the efficiency of this smart material, compounding of silicone rubber with various fillers can be carried out. The effect of organically modified montmorillonite (OMMT) nano-clay on improvement of dielectric properties, actuation stress and its relaxation response was considered in this study. OMMT was dispersed in room temperature vulcanized (RTV) silicone rubber, and a composite film was cast. Using an in-house actuation set-up, it was shown that the actuation stress for a given electric field intensity is higher for composites than that for pristine silicone rubber. Also, the time-dependent actuation response of the samples was evaluated, and it was shown that the characteristic relaxation time of the actuation stress for composites is less than for the pristine rubber as a result of OMMT addition.

  8. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

    SciTech Connect

    Ignarro, L.J.; Buga, G.M.; Wood, K.S.; Byrns, R.E.; Chaudhuri, G.

    1987-12-01

    The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is and unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. The authors have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were compared with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. Thus, EDRF released from artery and vein possesses identical and biological and chemical properties as NO.

  9. Substance P-induced relaxation and hyperpolarization in human cerebral arteries.

    PubMed Central

    Petersson, J.; Zygmunt, P. M.; Brandt, L.; Högestätt, E. D.

    1995-01-01

    1. Vascular effects of substance P were studied in human isolated pial arteries removed from 14 patients undergoing cerebral cortical resection. 2. Substance P induced a concentration-dependent relaxation in the presence of indomethacin. No relaxation was seen in arteries where the endothelium had been removed. 3. N omega-nitro-L-arginine (L-NOARG, 0.3 mM) abolished the relaxation in arteries from six patients. The relaxation was only partially inhibited in the remaining eight patients, the reduction of the maximum relaxation being less than 50% in each patient. 4. The L-NOARG-resistant relaxation was abolished when the external K+ concentration was raised above 30 mM. 5. Substance P caused a smooth muscle hyperpolarization (in the presence of L-NOARG and indomethacin), but only when the artery showed an L-NOARG-resistant relaxation. 6. The results indicate that nitric oxide is an important mediator of endothelium-dependent relaxation in human cerebral arteries. Furthermore, another endothelium-dependent pathway, causing hyperpolarization and vasodilatation, was identified in arteries from more than half the population of patients. PMID:7582516

  10. 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

  11. The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.

    PubMed

    Min, Chang Ho; Min, Young Sil; Lee, Sang Joon; Sohn, Uy Dong

    2016-06-01

    It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle. PMID:27260628

  12. Microscopic insight into the pump-probe relaxation dynamics of superconductors: Model study of MgB2relaxation within nonlinear response theory

    NASA Astrophysics Data System (ADS)

    Baňacký, Pavol; Szöcs, Vojtech

    2016-05-01

    Here we present a quantum-statistical formulation of third-order polarization P(3)(t), which is induced in a sample by a sequence of incident external fields, and serves as a source of an emitted radiation field detected as a signal in pump-probe (PP) experiments. Our treatment is based on the perturbation expansion of the non-equilibrium density matrix for calculation of multi-time correlation functions, and the corresponding response function, at finite temperature. As a model for our study, the high-temperature superconductor MgB2 has been selected. Knowledge of the electronic structure of the studied system, and of the corresponding Eliashberg function that represents pertinent electron-phonon (EP) interactions, enabled us to distinguish non-equilibrium processes running over different time-periods in a sequence of interactions with laser pulses on a microscopic level. We have also derived temperature-dependent relaxation dynamics as a function of delay time between the pump and probe pulses. For the studied model system of MgB2, we have shown that an abrupt increase of the relaxation time at Tc, as detected by experiments, is the direct consequence of sudden changes in the character of EP coupling in transition from an adiabatic to a stabilized superconducting anti-adiabatic state, as it predicts the anti-adiabatic theory of electron-vibration interactions. The BCS model, which preserves the adiabatic character of EP coupling also below the critical temperature of MgB2, is basically unable to reflect the enormous sudden increase of the relaxation time. Based on diagrammatic perturbation theory, differences in the optical pump-optical probe and the optical pump-terahertz probe settings of MgB2 PP relaxation dynamics are discussed.

  13. EFFECTS OF ENZYMATIC DEGRADATION ON THE FRICTIONAL RESPONSE OF ARTICULAR CARTILAGE IN STRESS RELAXATION

    PubMed Central

    Basalo, Ines M.; Raj, David; Krishnan, Ramaswamy; Chen, Faye H.; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    SUMMARY It was recently shown experimentally that the friction coefficient of articular cartilage correlates with the interstitial fluid pressurization, supporting the hypothesis that interstitial water pressurization plays a fundamental role in the frictional response by supporting most of the load during the early time response. A recent study showed that enzymatic treatment with chondroitinase ABC causes a decrease in the maximum fluid load support of bovine articular cartilage in unconfined compression. The hypothesis of this study is that treatment with chondroitinase ABC will increase the friction coefficient of articular cartilage in stress relaxation. Articular cartilage samples (n=34) harvested from the femoral condyles of five bovine knee joints (1–3 months-old) were tested in unconfined compression with simultaneous continuous sliding (±1.5 mm at 1 mm/s) under stress relaxation. Results showed a significantly higher minimum friction coefficient in specimens treated with 0.1 u/ml of chondroitinase ABC for 24 hours (μmin = 0.082 ± 0.024) compared to control specimens (μmin = 0.047 ± 0.014). Treated samples also exhibited higher equilibrium friction coefficient (μeq = 0.232 ± 0.049) than control samples (μeq = 0.184 ± 0.036), which suggest that the frictional response is greatly influenced by the degree of tissue degradation. The fluid load support was predicted from theory, and the maximum value (as a percentage of the total applied load) was lower in treated specimens (77 ± 12%) than in control specimens (85 ± 6%). Based on earlier findings, the increase in the ratio μmin/μeq may be attributed to the decrease in fluid load support. PMID:15863119

  14. Nonlinear structural response using adaptive dynamic relaxation on a massively-parallel-processing system

    NASA Technical Reports Server (NTRS)

    Oakley, David R.; Knight, Norman F., Jr.

    1994-01-01

    A parallel adaptive dynamic relaxation (ADR) algorithm has been developed for nonlinear structural analysis. This algorithm has minimal memory requirements, is easily parallelizable and scalable to many processors, and is generally very reliable and efficient for highly nonlinear problems. Performance evaluations on single-processor computers have shown that the ADR algorithm is reliable and highly vectorizable, and that it is competitive with direct solution methods for the highly nonlinear problems considered. The present algorithm is implemented on the 512-processor Intel Touchstone DELTA system at Caltech, and it is designed to minimize the extent and frequency of interprocessor communication. The algorithm has been used to solve for the nonlinear static response of two and three dimensional hyperelastic systems involving contact. Impressive relative speedups have been achieved and demonstrate the high scalability of the ADR algorithm. For the class of problems addressed, the ADR algorithm represents a very promising approach for parallel-vector processing.

  15. Relaxation method and TCLE method of linear response in terms of thermo-field dynamics

    NASA Astrophysics Data System (ADS)

    Saeki, Mizuhiko

    2008-03-01

    The general formulae of the dynamic susceptibility are derived using the relaxation method and the TCLE method for the linear response by introducing the renormalized hat-operator in terms of thermo-field dynamics (TFD). In the former method, the Kubo formula is calculated for systems with no external driving fields, while in the latter method the admittance is directly calculated from time-convolutionless equations with external driving terms. The relation between the two methods is analytically investigated, and also the fluctuation-dissipation theorem is examined for the two methods in terms of TFD. The TCLE method is applied to an interacting spin system, and a formula of the transverse magnetic susceptibility is derived for such a system. The transverse magnetic susceptibility of an interacting spin system with S = 1 / 2 spins is obtained up to the first order in powers of the spin-spin interaction.

  16. Stress-relaxation response of human menisci under confined compression conditions.

    PubMed

    Martin Seitz, Andreas; Galbusera, Fabio; Krais, Carina; Ignatius, Anita; Dürselen, Lutz

    2013-10-01

    The objective of this study was to determine the viscoelastic properties of human meniscal tissue during stress-relaxation under confined compression conditions. Lateral and medial longitudinal meniscus plugs of 25 donor knees (ntotal=150) were exposed to stress-relaxation tests under confined compression conditions at three compression levels (ε=0.1; 0.15; 0.2). Mathematical modelling using an exponential 1D-diffusion equation was used to predict the viscoelastic properties. Subsequently, finite element (FE) models were created using identical geometry, properties and test conditions as used for the in-vitro tests. Two constitutively different underlying mathematical formulations were applied to the FE models to reveal possible differences in their predictions for the relaxation response. While the first FE model mimicked the analytical model (FE1), the second FE model used a different biphasic, non-linear approach (FE2). Regression analyses showed promising coefficients of determination (R(2)>0.73) between the experimental data and the predictions obtained from the diffusion equation and the two FE models. Mean aggregate modulus, predicted with the diffusion equation (HA=64.0 kPa) was lower than those obtained with the two FE analyses (HA,FE1=91.9 kPa; HA,FE2=81.5 kPa). Mean hydraulic permeability (kFE2=1.5×10(-15)m(4)/Ns) of the second FE2 approach was statistically lower (p<0.01) than the other permeability values (k=3.9×10(-15)m(4)/Ns; kFE1=3.4×10(-15)m(4)/Ns). These differences are mainly due to the different underlying mathematical models used. However, when compared with corresponding literature, the results of the present study indicated good agreement. The results of the present study contribute to a better understanding of the complex nature of meniscal tissue and might also have an impact on the design of future meniscal substitutes. PMID:23811278

  17. Induced tolerance expressed as relaxed behavioural threat response in millimetre-sized aquatic organisms

    PubMed Central

    Hylander, Samuel; Ekvall, Mikael T.; Bianco, Giuseppe; Yang, Xi; Hansson, Lars-Anders

    2014-01-01

    Natural selection shapes behaviour in all organisms, but this is difficult to study in small, millimetre-sized, organisms. With novel labelling and tracking techniques, based on nanotechnology, we here show how behaviour in zooplankton (Daphnia magna) is affected by size, morphology and previous exposure to detrimental ultraviolet radiation (UVR). All individuals responded with immediate downward swimming to UVR exposure, but when released from the threat they rapidly returned to the surface. Large individuals swam faster and generally travelled longer distances than small individuals. Interestingly, individuals previously exposed to UVR (during several generations) showed a more relaxed response to UVR and travelled shorter total distances than those that were naive to UVR, suggesting induced tolerance to the threat. In addition, animals previously exposed to UVR also had smaller eyes than the naive ones, whereas UVR-protective melanin pigmentation of the animals was similar between populations. Finally, we show that smaller individuals have lower capacity to avoid UVR which could explain patterns in natural systems of lower migration amplitudes in small individuals. The ability to change behavioural patterns in response to a threat, in this case UVR, adds to our understanding of how organisms navigate in the ‘landscape of fear’, and this has important implications for individual fitness and for interaction strengths in biotic interactions. PMID:24966309

  18. Characterisation of the response of equine digital arteries and veins to substance P.

    PubMed

    Katz, L M; Marr, C M; Elliott, J

    2003-10-01

    Substance P (SP), a potent vasodilator, has been detected in equine digital sensory-motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre-constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium- and concentration-dependent manner to SP. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; 300 microm) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely L-NAME-resistant, whereas the second phase was inhibited by 60%. Both L-NAME and a cyclo-oxygenase inhibitor (ibuprofen; 10 microm) were required to inhibit EDV relaxation to SP by > or =80%. Experiments determining the receptor mediated responses to physiological concentrations of SP (1 nm) revealed that the relaxant responses of both EDA and EDV were inhibited by a neurokinin-1 (NK1) receptor antagonist (CP-96 345; 10 nm). In conclusion, SP is an endothelium-dependent vasodilator of both EDA and EDV. NO is the predominant pathway activated in EDA, whereas both prostacyclin and NO pathways are involved in EDVs. NK1 receptors appear to mediate responses to low concentrations of SP. PMID:14633189

  19. Predicting Differential Response to EMG Biofeedback and Relaxation Training: The Role of Cognitive Structure.

    ERIC Educational Resources Information Center

    Hart, James D.

    1984-01-01

    Analyzed treatment outcome data for 102 headache patients who had been assigned randomly to receive either EMG biofeedback (N=70) or relaxation training (N=32). Analysis demonstrated that relaxation training was significantly more effective than biofeedback and that mixed headache patients improved significantly less than either migraine or…

  20. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    PubMed

    Bhasin, Manoj K; Dusek, Jeffery A; Chang, Bei-Hung; Joseph, Marie G; Denninger, John W; Fricchione, Gregory L; Benson, Herbert; Libermann, Towia A

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress. PMID:23650531

  1. Response of turbulence subjected to a straining-relaxation-destraining cycle

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Meneveau, Charles; Katz, Joseph

    2004-11-01

    The response of turbulence subjected to planar straining and de-straining is studied experimentally, and the impact of the applied distortions on the energy transfer across different length scales is quantified. The data are obtained using Planar Particle Image Velocimetry (PIV) in a water tank, in which high Reynolds number turbulence with very low mean velocity is generated by an array of spinning grids. Planar straining and de-straining mean flows are produced by pushing and pulling a rectangular piston towards, and away from, the bottom wall of the tank. The data are processed to yield the time evolution of Reynolds stresses, anisotropy tensors, turbulence kinetic energy production, and mean subgrid dissipation rate at various scales. During straining, the production rises rapidly. After the relaxation period the small-scale SGS stresses recover isotropy, but the Reynolds stresses at large scales still display significant anisotropy. When destraining is applied, a strong negative production (back-scattering) is observed, by which turbulence fluctuations return kinetic energy to the mean flow. Reversed energy transfer is also revealed in the vorticity fluctuations history. The experiment allows to disentangle in detail the causes for this global backscatter phenomenon in terms of non-equilibrium conditions of the Reynolds stresses, and to follow the trends as function of scale.

  2. Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization

    PubMed Central

    Stahl, James E.; Dossett, Michelle L.; LaJoie, A. Scott; Denninger, John W.; Mehta, Darshan H.; Goldman, Roberta; Fricchione, Gregory L.; Benson, Herbert

    2015-01-01

    Background Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. Objective Estimate the effect of mind body training, specifically, the Relaxation Response Resiliency Program (3RP) on healthcare utilization. Design Retrospective controlled cohort observational study. Setting: Major US Academic Health Network. Sample: All patients receiving 3RP at the MGH Benson-Henry Institute from 1/12/2006 to 7/1/2014 (n = 4452), controls (n = 13149) followed for a median of 4.2 years (.85–8.4 yrs). Measurements: Utilization as measured by billable encounters/year (be/yr) stratified by encounter type: clinical, imaging, laboratory and procedural, by class of chief complaint: e.g., Cardiovascular, and by site of care delivery, e.g., Emergency Department. Subgroup analysis by propensity score matched pre-intervention utilization rate. Results At one year, total utilization for the intervention group decreased by 43% [53.5 to 30.5 be/yr] (p <0.0001). Clinical encounters decreased by 41.9% [40 to 23.2 be/yr], imaging by 50.3% [11.5 to 5.7 be/yr], lab encounters by 43.5% [9.8 to 5.6], and procedures by 21.4% [2.2 to 1.7 be/yr], all p < 0.01. The intervention group’s Emergency department (ED) visits decreased from 3.6 to 1.7/year (p<0.0001) and Hospital and Urgent care visits converged with the controls. Subgroup analysis (identically matched initial utilization rates—Intervention group: high utilizing controls) showed the intervention group significantly reduced utilization relative to the control group by: 18.3% across all functional categories, 24.7% across all site categories and 25.3% across all clinical categories. Conclusion Mind body interventions such as 3RP have the potential to substantially reduce healthcare utilization at

  3. Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model

    PubMed Central

    Singh, Sheela P.; Lu, Chunhua; Han, Lin; Hobbs, Brian P.; Pradeep, Sunila; Choi, Hyun J.; Bankson, James A.

    2015-01-01

    Purpose To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed. Results Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T1 relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis. Conclusions Findings suggest that increased tumor T1 relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response. PMID:26098849

  4. Integrating a Relaxation Response-Based Curriculum into a Public High School in Massachusetts

    ERIC Educational Resources Information Center

    Foret, Megan M.; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R.

    2012-01-01

    Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes…

  5. Relaxation Training and Opioid Inhibition of Blood Pressure Response to Stress.

    ERIC Educational Resources Information Center

    McCubbin, James A.; And Others

    1996-01-01

    Sought to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Subjects were 32 young men with mildly elevated casual arterial pressure. Assessed opioid mechanisms by examining the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and…

  6. Analysis of the role of nitric oxide in the relaxant effect of the crude extract and fractions from Eugenia uniflora in the rat thoracic aorta.

    PubMed

    Wazlawik, E; Da Silva, M A; Peters, R R; Correia, J F; Farias, M R; Calixto, J B; Ribeiro-Do-Valle, R M

    1997-04-01

    This study has evaluated the possible role played by the L-arginine-nitric oxide pathway in the vasorelaxant action of the hydroalcoholic extract from Eugenia uniflora, and fractions from the extract, in rings of rat thoracic aorta. The addition of an increasing cumulative concentration of hydroalcoholic extract from E. uniflora (1-300 micrograms mL-1) caused a concentration-dependent relaxation response in intact endothelium-thoracic aorta rings pre-contracted with noradrenaline (30-100 nM). The IC50 value, with its respective confidence limit, and the maximum relaxation (Rmax) were 7.02 (4.77-10.00) micrograms mL-1 and 83.94 +/- 3.04%, respectively. The removal of the endothelium completely abolished these responses. The nitric oxide synthase inhibitors N omega-nitro-L-arginine (L-NOARG, 30 microM) and N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM), inhibited the relaxation (Rmax) to -10.43 +/- 7.81% and -3.69 +/- 2.62%, respectively. In addition, L-arginine (1 mM), but not D-arginine (1 mM), completely reversed inhibition by L-NOARG. Methylene blue (30 microM), a soluble guanylate cyclase inhibitor, reduced the relaxation induced by the extract to 14.60 +/- 7.40%. These data indicate that in the rat thoracic aorta the hydroalcoholic extract, and its fractions, from the leaves of E. uniflora have graded and endothelium-dependent vasorelaxant effects. PMID:9232544

  7. GAG depletion increases the stress-relaxation response of tendon fascicles, but does not influence recovery

    PubMed Central

    Legerlotz, Kirsten; Riley, Graham P.; Screen, Hazel R.C.

    2013-01-01

    Cyclic and static loading regimes are commonly used to study tenocyte metabolism in vitro and to improve our understanding of exercise-associated tendon pathologies. The aims of our study were to investigate if cyclic and static stress relaxation affected the mechanical properties of tendon fascicles differently, if this effect was reversible after a recovery period, and if the removal of glycosaminoglycans (GAGs) affected sample recovery. Tendon fascicles were dissected frombovine-foot extensors and subjected to 14% cyclic (1 Hz) or static tensile strain for 30 min. Additional fascicles were incubated overnight in buffer with 0.5 U chondroitinase ABC or in buffer alone prior to the static stress-relaxation regime. To assess the effect of different stress-relaxation regimes, a quasi-static test to failure was carried out, either directly post loading or after a 2 h recovery period, and compared with unloaded control fascicles. Both stress-relaxation regimes led to a significant reduction in fascicle failure stress and strain, but this was more pronounced in the cyclically loaded specimens. Removal of GAGs led to more stress relaxation and greater reductions in failure stress after static loading compared to controls. The reduction in mechanical properties was partially reversible in all samples, given a recovery period of 2 h. This has implications for mechanical testing protocols, as a time delay between fatiguing specimens and characterization of mechanical properties will affect the results. GAGs appear to protect tendon fascicles from fatigue effects, possibly by enabling sample hydration. PMID:23462553

  8. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  9. Possible involvement of ATP-sensitive K+ channels in the relaxant response of dog middle cerebral artery to cromakalim

    SciTech Connect

    Masuzawa, K.; Asano, M.; Matsuda, T.; Imaizumi, Y.; Watanabe, M. )

    1990-11-01

    To determine the functions of ATP-sensitive K+ (KATP) channels in cerebral arterial smooth muscle, the effects of cromakalim, an opener of these channels, on tension and 86Rb efflux were investigated in endothelium-removed strips of dog middle cerebral arteries (MCAs). Cromakalim relaxed the strips that were precontracted with 20.9 mM K+ with a small maximum response. The relaxant responses to cromakalim were competitively antagonized by glibenclamide, a blocker of KATP channels. In strips precontracted with 65.9 mM K+, cromakalim failed to relax the strips. The addition of cromakalim to a resting strip caused a dose-dependent relaxation. In the resting strips of MCAs preloaded with 86Rb, cromakalim did not increase the 86Rb efflux. With 42K as the tracer ion, cromakalim still had no effect on the efflux from the resting strips. On the other hand, cromakalim increased the 86Rb and 42K efflux from the strips of dog coronary arteries (CAs). In 20.9 mM K(+)-contracted strips of MCAs, cromakalim significantly decreased the 86Rb efflux. However, after the inactivation of Ca(++)-activated K+ channels by the addition of 1 x 10(-7) M nifedipine to the 20.9 mM K(+)-contracted strips of MCAs, cromakalim produced a small but significant increase in the 86Rb efflux. Similarly, when the resting strips of MCAs were placed in the Ca(++)-free 12 mM-Mg(+)+ solution, cromakalim increased the 86Rb efflux. In 65.9 mM K(+)-contracted strips, cromakalim increased the 86Rb efflux from both arteries. However, the extent of the increase in 86Rb efflux was significantly smaller in the MCA than in the CA.

  10. Studies of the role of endothelium-dependent nitric oxide release in the sustained vasodilator effects of corticotrophin releasing factor and sauvagine.

    PubMed

    Barker, D M; Corder, R

    1999-01-01

    1. The mechanisms of the sustained vasodilator actions of corticotrophin-releasing factor (CRF) and sauvagine (SVG) were studied using rings of endothelium de-nuded rat thoracic aorta (RTA) and the isolated perfused rat superior mesenteric arterial vasculature (SMA). 2. SVG was approximately 50 fold more potent than CRF on RTA (EC40: 0.9 +/- 0.2 and 44 +/- 9 nM respectively, P < 0.05), and approximately 10 fold more active in the perfused SMA (ED40: 0.05 +/- 0.02 and 0.6 +/- 0.1 nmol respectively, P < 0.05). Single bolus injections of CRF (100 pmol) or SVG (15 pmol) in the perfused SMA caused reductions in perfusion pressure of 23 +/- 1 and 24 +/- 2% that lasted more than 20 min. 3. Removal of the endothelium in the perfused SMA with deoxycholic acid attenuated the vasodilatation and revealed two phases to the response; a short lasting direct action, and a sustained phase which was fully inhibited. 4. Inhibition of nitric oxide synthase with L-NAME (100 microM) L-NMMA (100 microM) or 2-ethyl-2-thiopseudourea (ETPU, 100 microM) had similar effects on the vasodilator responses to CRF as removal of the endothelium, suggesting a pivotal role for nitric oxide. However the selective guanylate cyclase inhibitor 1H-[l,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 10 microM) did not affect the response to CRF. 5. High potassium (60 mM) completely inhibited the vasodilator response to CRF in the perfused SMA, indicating a role for K channels in this response. 6. Compared to other vasodilator agents acting via the release of NO, the actions of CRF and SVG are strikingly long-lasting, suggesting a novel mechanism of prolonged activation of nitric oxide synthase. PMID:10051151

  11. Prostaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase.

    PubMed

    Hristovska, Ana-Marija; Rasmussen, Lasse E; Hansen, Pernille B L; Nielsen, Susan S; Nüsing, Rolf M; Narumiya, Shuh; Vanhoutte, Paul; Skøtt, Ole; Jensen, Boye L

    2007-09-01

    The present experiments were designed to test the hypothesis that prostaglandin (PG) E(2) causes vasodilatation through activation of endothelial NO synthase (eNOS). Aortic rings from mice with targeted deletion of eNOS and E-prostanoid (EP) receptors were used for contraction studies. Blood pressure changes in response to PGE(2) were measured in conscious mice. Single doses of PGE(2) caused concentration-dependent relaxations during contractions to phenylephrine (EC(50)=5*10(-8) mol/L). Relaxation after PGE(2) was absent in rings without endothelium and in rings from eNOS(-/-) mice and was abolished by N(G)-nitro-l-arginine methyl ester and the soluble guanylate cyclase inhibitor 1H(1,2,4)-oxadiazolo-[4,3-a]quinoxalin-1-one. In PGE(2)-relaxed aortic rings, the cGMP content increased significantly. PGE(2)-induced relaxations were abolished by the EP4 receptor antagonist AE3-208 (10(-8) mol/L) and mimicked by an EP4 agonist (AE1-329, 10(-7) mol/L) in the presence of endothelium and eNOS only. Relaxations were attenuated significantly in rings from EP4(-/-) mice but normal in EP2(-/-). Inhibitors of the cAMP-protein kinase A pathway attenuated, whereas the inhibitor of protein phosphatase 1C, calyculin (10(-8) mol/L), abolished the PGE(2)-mediated relaxation. In aortic rings, PGE(2) dephosphorylated eNOS at Thr(495). Chronically catheterized eNOS(-/-) mice were hypertensive (137+/-3.6 mm Hg, n=13, versus 101+/-3.9 mm Hg, n=9) and exhibited a lower sensitivity of blood pressure reduction in response to PGE(2) compared with wild-type mice. There was no difference in the blood pressure response to nifedipine. These findings show that PGE(2) elicits EP4 receptor-mediated, endothelium-dependent stimulation of eNOS activity by dephosphorylation at Thr(495) resulting in guanylyl cyclase-dependent vasorelaxation and accumulation of cGMP in aortic rings. PMID:17635857

  12. Studies of the role of endothelium-dependent nitric oxide release in the sustained vasodilator effects of corticotrophin releasing factor and sauvagine

    PubMed Central

    Barker, Diana M; Corder, Roger

    1999-01-01

    The mechanisms of the sustained vasodilator actions of corticotrophin-releasing factor (CRF) and sauvagine (SVG) were studied using rings of endothelium de-nuded rat thoracic aorta (RTA) and the isolated perfused rat superior mesenteric arterial vasculature (SMA).SVG was ≈amp;50 fold more potent than CRF on RTA (EC40: 0.9±0.2 and 44±9 nM respectively, P<0.05), and ≈amp;10 fold more active in the perfused SMA (ED40: 0.05±0.02 and 0.6±0.1 nmol respectively, P<0.05). Single bolus injections of CRF (100 pmol) or SVG (15 pmol) in the perfused SMA caused reductions in perfusion pressure of 23±1 and 24±2% that lasted more than 20 min.Removal of the endothelium in the perfused SMA with deoxycholic acid attenuated the vasodilatation and revealed two phases to the response; a short lasting direct action, and a sustained phase which was fully inhibited.Inhibition of nitric oxide synthase with L-NAME (100 μM) L-NMMA (100 μM) or 2-ethyl-2-thiopseudourea (ETPU, 100 μM) had similar effects on the vasodilator responses to CRF as removal of the endothelium, suggesting a pivotal role for nitric oxide. However the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM) did not affect the response to CRF.High potassium (60 mM) completely inhibited the vasodilator response to CRF in the perfused SMA, indicating a role for K+ channels in this response.Compared to other vasodilator agents acting via the release of NO, the actions of CRF and SVG are strikingly long-lasting, suggesting a novel mechanism of prolonged activation of nitric oxide synthase. PMID:10051151

  13. Childhood Trauma and Neural Responses to Personalized Stress, Favorite-Food and Neutral-Relaxing Cues in Adolescents

    PubMed Central

    Elsey, James; Coates, Alice; Lacadie, Cheryl M; McCrory, Eamon J; Sinha, Rajita; Mayes, Linda C; Potenza, Marc N

    2015-01-01

    Previous studies have found childhood trauma to be associated with functional and structural abnormalities in corticostriatal-limbic brain regions, which may explain the associations between trauma and negative mental and physical health outcomes. However, functional neuroimaging of maltreatment-related trauma has been limited by largely using generic and predominantly aversive stimuli. Personalized stress, favorite-food, and neutral/relaxing cues during functional magnetic resonance imaging were used to probe the neural correlates of emotional/motivational states in adolescents with varying exposure to maltreatment-related trauma. Sixty-four adolescents were stratified into high- or low-trauma-exposed groups. Cue-related measures of subjective anxiety and craving were collected. Relative to the low-trauma-exposed group, high-trauma-exposed adolescents displayed an increased activation of insula, anterior cingulate, and prefrontal cortex in response to stress cues. Activation in subcortical structures, including the hippocampus, was inversely correlated with subjective anxiety in the high- but not the low-trauma-exposed group. The high-trauma-exposed group displayed hypoactivity of cerebellar regions in response to neutral/relaxing cues. No group differences were observed in response to favorite-food cues. The relationship between trauma exposure and altered cortico-limbic circuitry may in part explain the association between childhood trauma and heightened vulnerability to emotional disturbances and risky behaviour. This may be particularly pertinent during adolescence when such difficulties often emerge. Further work is needed to elucidate the mechanism linking trauma to obesity. PMID:25567424

  14. Childhood trauma and neural responses to personalized stress, favorite-food and neutral-relaxing cues in adolescents.

    PubMed

    Elsey, James; Coates, Alice; Lacadie, Cheryl M; McCrory, Eamon J; Sinha, Rajita; Mayes, Linda C; Potenza, Marc N

    2015-06-01

    Previous studies have found childhood trauma to be associated with functional and structural abnormalities in corticostriatal-limbic brain regions, which may explain the associations between trauma and negative mental and physical health outcomes. However, functional neuroimaging of maltreatment-related trauma has been limited by largely using generic and predominantly aversive stimuli. Personalized stress, favorite-food, and neutral/relaxing cues during functional magnetic resonance imaging were used to probe the neural correlates of emotional/motivational states in adolescents with varying exposure to maltreatment-related trauma. Sixty-four adolescents were stratified into high- or low-trauma-exposed groups. Cue-related measures of subjective anxiety and craving were collected. Relative to the low-trauma-exposed group, high-trauma-exposed adolescents displayed an increased activation of insula, anterior cingulate, and prefrontal cortex in response to stress cues. Activation in subcortical structures, including the hippocampus, was inversely correlated with subjective anxiety in the high- but not the low-trauma-exposed group. The high-trauma-exposed group displayed hypoactivity of cerebellar regions in response to neutral/relaxing cues. No group differences were observed in response to favorite-food cues. The relationship between trauma exposure and altered cortico-limbic circuitry may in part explain the association between childhood trauma and heightened vulnerability to emotional disturbances and risky behaviour. This may be particularly pertinent during adolescence when such difficulties often emerge. Further work is needed to elucidate the mechanism linking trauma to obesity. PMID:25567424

  15. Whole blood viscosity and erythrocyte deformability are related to endothelium-dependent vasodilation and coronary risk in the elderly. The prospective investigation of the vasculature in Uppsala seniors (PIVUS) study.

    PubMed

    Sandhagen, Bo; Lind, Lars

    2012-01-01

    It has previously been shown that a high hemoglobin value, a major determinant of whole blood viscosity (WBV), predicts cardiovascular events. One putative mechanism might be an impaired endothelial function. Erythrocyte deformability is another rheologic feature of the erythrocyte being of importance for the flow properties of the blood, especially in the capillaries. The present study evaluates the relationships between blood viscosity, erythrocyte deformability assessed as erythrocyte fluidity (EF), coronary risk and endothelial vasodilatory function. In the population-based PIVUS study (1016 subjects aged 70); endothelium-dependent vasodilation (EDV) was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). WBV, plasma viscosity (PV) and EF were measured in a random sample of 573 subjects. WBV and PV were positively and EF negatively related to Framingham risk score. EDV was inversely related to both whole blood and plasma viscosity. FMD was not related to any rheologic variable. In multiple regression analyses WBV and EF were significantly related to EDV independently of gender, hypertension, smoking, hypercholesterolemia, obesity and diabetes. Acetylcholine-induced vasodilation in the forearm, but not FMD, was negatively related to whole blood viscosity and positively related to EF independently of traditional risk factors in elderly subjects, indicating a pathophysiological link between impaired hemorheology and coronary risk. PMID:22240364

  16. Perturbation of chemical coupling by an endothelial Cx40 mutant attenuates endothelium-dependent vasodilation by KCa channels and elevates blood pressure in mice.

    PubMed

    Chaston, Daniel J; Haddock, Rebecca E; Howitt, Lauren; Morton, Susan K; Brown, Russell D; Matthaei, Klaus I; Hill, Caryl E

    2015-09-01

    Mutant forms of connexin40 (Cx40) exist in the human population and predispose carriers to atrial fibrillation. Since endothelial expression of Cx40 is important for electrical and chemical communication within the arterial wall, carriers of mutant Cx40 proteins may be predisposed to peripheral arterial dysfunction and dysregulation of blood pressure. We have therefore studied mice expressing either a chemically dysfunctional mutant, Cx40T202S, or wild-type Cx40, with native Cx40, specifically in the endothelium. Blood pressure was measured by telemetry under normal conditions and during cardiovascular stress induced by locomotor activity, phenylephrine or nitric oxide blockade (N(ɷ)-nitro-L-arginine methyl ester hydroxide, L-NAME). Blood pressure of Cx40T202STg mice was significantly elevated at night when compared with wild-type or Cx40Tg mice, without change in mean heart rate, pulse pressure or locomotor activity. Analysis over 24 h showed that blood pressure of Cx40T202STg mice was significantly elevated at rest and additionally during locomotor activity. In contrast, neither plasma renin concentration nor pressor responses to phenylephrine or L-NAME were altered, the latter indicating that nitric oxide bioavailability was normal. In isolated, pressurised mesenteric arteries, hyperpolarisation and vasodilation evoked by SKA-31, the selective modulator of SKCa and IKCa channels, was significantly reduced in Cx40T202STg mice, due to attenuation of the SKCa component. Acetylcholine-induced ascending vasodilation in vivo was also significantly attenuated in cremaster muscle arterioles of Cx40T202STg mice, compared to wild-type and Cx40Tg mice. We conclude that endothelial expression of the chemically dysfunctional Cx40T202S reduces peripheral vasodilator capacity mediated by SKCa-dependent hyperpolarisation and also increases blood pressure. PMID:25369777

  17. Effectiveness of the Relaxation Response-Based Group Intervention for Treating Depressed Chinese American Immigrants: A Pilot Study

    PubMed Central

    Yeung, Albert; Slipp, Lauren E.; Niles, Halsey; Jacquart, Jolene; Chow, Choi-Ling; Fava, Maurizio; Denninger, John W.; Benson, Herbert; Fricchione, Gregory L.

    2014-01-01

    Background: This study examined the feasibility, safety and efficacy of an 8-week Relaxation Response (RR)-based group. Methods: Twenty-two depressed Chinese American immigrants were recruited. Outcomes measures were response and remission rates, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and the Multidimensional Scale of Perceived Social Support Scale. Results: Participants (N = 22) were 82% female, mean age was 53 (±12). After intervention, completers (N = 15) showed a 40% response rate and a 27% remission rate, and statistically significant improvement in most outcome measures. Discussion: The RR-based group is feasible and safe in treating Chinese American immigrants with depression. PMID:25198683

  18. Structure–Redox–Relaxivity Relationships for Redox Responsive Manganese-Based Magnetic Resonance Imaging Probes

    PubMed Central

    2015-01-01

    A library of 10 Mn-containing complexes capable of switching reversibly between the Mn(II) and Mn(III) oxidation states was prepared and evaluated for potential usage as MRI reporters of tissue redox activity. We synthesized N-(2-hydroxybenzyl)-N,N′,N′-ethylenediaminetriacetic acid (HBET) and N-(2-hydroxybenzyl-N,N′,N′-trans-1,2-cyclohexylenediaminetriacetic acid (CyHBET) ligands functionalized (−H, −OMe, −NO2) at the 5-position of the aromatic ring. The Mn(II) complexes of all ligands and the Mn(III) complexes of the 5-H and 5-NO2 functionalized ligands were synthesized and isolated, but the Mn(III) complexes with the 5-OMe functionalized ligands were unstable. 1H relaxivity of the 10 isolable complexes was measured at pH 7.4 and 37 °C, 1.4 T. Thermodynamic stability, pH-dependent complex speciation, hydration state, water exchange kinetics of the Mn(II) complexes, and pseudo-first order reduction kinetics of the Mn(III) complexes were studied using a combination of pH-potentiometry, UV–vis spectroscopy, and 1H and 17O NMR measurements. The effects of ligand structural and electronic modifications on the Mn(II/III) redox couple were studied by cyclic voltammetry. The Mn(II) complexes are potent relaxation agents as compared to the corresponding Mn(III) species with [MnII(CyHBET)(H2O)]2– exhibiting a 7.5-fold higher relaxivity (3.3 mM–1 s–1) than the oxidized form (0.4 mM–1 s–1). At pH 7.4, Mn(II) exists as a mixture of fully deprotonated (ML) and monoprotonated (HML) complexes and Mn(II) complex stability decreases as the ligands become more electron-releasing (pMn for 10 μM [MnII(CyHBET–R′)(H2O)]2– decreases from 7.6 to 6.2 as R′ goes from −NO2 to −OMe, respectively). HML speciation increases as the electron-releasing nature of the phenolato-O donor increases. The presence of a water coligand is maintained upon conversion from HML to ML, but the water exchange rate of ML is faster by up to 2 orders of magnitude (kex310 for

  19. Structure-relaxation mechanism for the response of T4 lysozyme cavity mutants to hydrostatic pressure.

    PubMed

    Lerch, Michael T; López, Carlos J; Yang, Zhongyu; Kreitman, Margaux J; Horwitz, Joseph; Hubbell, Wayne L

    2015-05-12

    Application of hydrostatic pressure shifts protein conformational equilibria in a direction to reduce the volume of the system. A current view is that the volume reduction is dominated by elimination of voids or cavities in the protein interior via cavity hydration, although an alternative mechanism wherein cavities are filled with protein side chains resulting from a structure relaxation has been suggested [López CJ, Yang Z, Altenbach C, Hubbell WL (2013) Proc Natl Acad Sci USA 110(46):E4306-E4315]. In the present study, mechanisms for elimination of cavities under high pressure are investigated in the L99A cavity mutant of T4 lysozyme and derivatives thereof using site-directed spin labeling, pressure-resolved double electron-electron resonance, and high-pressure circular dichroism spectroscopy. In the L99A mutant, the ground state is in equilibrium with an excited state of only ∼ 3% of the population in which the cavity is filled by a protein side chain [Bouvignies et al. (2011) Nature 477(7362):111-114]. The results of the present study show that in L99A the native ground state is the dominant conformation to pressures of 3 kbar, with cavity hydration apparently taking place in the range of 2-3 kbar. However, in the presence of additional mutations that lower the free energy of the excited state, pressure strongly populates the excited state, thereby eliminating the cavity with a native side chain rather than solvent. Thus, both cavity hydration and structure relaxation are mechanisms for cavity elimination under pressure, and which is dominant is determined by details of the energy landscape. PMID:25918400

  20. Cardiovascular responses to isometric hand grip vs. relaxed hand grip in sustained cycling efforts.

    PubMed

    Canivel, Randy G; Wyatt, Frank B; Baker, Julien S

    2012-11-01

    Peripheral isometric contractions may lead to enhanced performance. Previous research using hand grip protocols indicates increased stabilization and peak power outputs. Research is lacking with the grip vs. no-grip protocol during sustained efforts. The purpose of this study is to determine cardiovascular reactions (i.e., heart rate [HR], blood pressure [BP], and rate pressure product [RPP]) during sustained cycling via an isometric and relaxed hand grip. Nine (n = 9) recreational cyclists participated in this study. After signing a medical and physical readiness questionnaire, the subjects were randomly assigned to 1 of 2 different protocols. Preexercising values of the HR (beats per minute), BP (miilimeters of mercury), height (centimeters), weight (kilograms), and age (years) were assessed before testing. A Monark bicycle ergometer was used for testing. Grip was substantiated through the use of a hand grip dynamometer at 20 kg of tension. Protocol 1 used an isometric "Hand Grip" scenario at 150 W for 20 minutes. Protocol 2 used a "Relaxed Hand Grip" at the same power and time. During the 20-minute exercise test, HR (POLAR), BP (stethoscope and sphygmomanometer), and calculated RPP (HR × systolic BP [SPB]/100) were recorded every minute. Statistical measures included mean and SDs between protocols, and dependent samples t-tests were used to examine differences between grip and no-grip protocols. At an alpha of ≤0.05, SBP did show a significant increase when using no grip, 161.4 (5.1) mm Hg vs. grip, 154.1 (6.6) mm Hg. However, rate pressure product and heart rate showed no significant differences between protocols. Our data suggested that the use of an isometric hand grip is transient and diminishes over time. PMID:22105053

  1. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise

    NASA Astrophysics Data System (ADS)

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-01

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration.A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic

  2. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise.

    PubMed

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-14

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration. PMID:27103542

  3. Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome—an analysis from RELAX-AHF

    PubMed Central

    Voors, Adriaan A; Davison, Beth A; Teerlink, John R; Felker, G Michael; Cotter, Gad; Filippatos, Gerasimos; Greenberg, Barry H; Pang, Peter S; Levin, Bruce; Hua, Tsushung A; Severin, Thomas; Ponikowski, Piotr; Metra, Marco

    2014-01-01

    Aims We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF). Methods and results RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40 mg] + [(total oral dose)/80 mg)] furosemide (or equivalent loop diuretic dose) up to day 5. Median diuretic response was −0.42 (−1.00, −0.14) kg/40 mg. A poor diuretic response was independently associated with Western-like region (Western Europe, North America, Israel, and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels of aspartate aminotransferase and potassium (all P < 0.01). Randomization to serelaxin was associated with lower doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue scale (VAS) at day 5 (primary endpoint; P = 0.0002), and with a higher risk of cardiovascular death or rehospitalization for heart failure or renal failure through day 60 (secondary endpoint, P < 0.0001), but not with increased 180-day cardiovascular mortality (P = 0.507). Conclusions In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response. Trial registration: NCT00520806 PMID:25287144

  4. Relaxant and contractile responses of detrusor muscle strips obtained from bladder outlet-obstructed rats treated with doxazosin enantiomers.

    PubMed

    Wang, Miao; Ren, Xue-Jiao; Zhao, Qing-Hua; Lin, Li-Xin; Wang, Xue; Zhao, Yan; Ren, Lei-Ming

    2011-12-01

    (-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)(-1)·day(-1) for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (-)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (-)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats. PMID:22115277

  5. A Comparison of Relaxation Strategies.

    ERIC Educational Resources Information Center

    Matthews, Doris B.

    Some researchers argue that all relaxation techniques produce a single relaxation response while others support a specific-effects hypothesis which suggests that progressive relaxation affects the musculoskeletal system and that guided imagery affects cognitive changes. Autogenics is considered a technique which is both somatic and cognitive. This…

  6. Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.

    PubMed Central

    Yokota, Y; Imaizumi, Y; Asano, M; Matsuda, T; Watanabe, M

    1994-01-01

    1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812628

  7. Physiological Predictors of Response to Exposure, Relaxation, and Rescripting Therapy for Chronic Nightmares in a Randomized Clinical Trial

    PubMed Central

    Davis, Joanne L.; Rhudy, Jamie L.; Pruiksma, Kristi E.; Byrd, Patricia; Williams, Amy E.; McCabe, Klanci M.; Bartley, Emily J.

    2011-01-01

    Study Objectives: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy(ERRT) and extended prior research by including broad measures of mental health difficulties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. Methods: Forty-seven individuals were randomized to treatment or waitlist control. Results: The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, significant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. Conclusions: Findings provide additional support for the use of ERRT in treating nightmares and related difficulties and improving sleep. Citation: Davis JL; Rhudy JL; Pruiksma KE; Byrd P; Williams AE; McCabe KM; Bartley EJ. Physiological predictors of response to exposure, relaxation, and rescripting therapy for chronic nightmares in a randomized clinical trial. J Clin Sleep Med 2011;7(6):622-631. PMID:22171201

  8. Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

    PubMed Central

    Conger, J D; Robinette, J B; Schrier, R W

    1988-01-01

    Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels. PMID:3261301

  9. Relaxed Intensity

    ERIC Educational Resources Information Center

    Ramey, Kyle

    2004-01-01

    Relaxed intensity refers to a professional philosophy, demeanor, and way of life. It is the key to being an effective educational leader. To be successful one must be relaxed, which means managing stress efficiently, having fun, and enjoying work. Intensity allows one to get the job done and accomplish certain tasks or goals. Educational leaders…

  10. Impedance response and dielectric relaxation in co-precipitation derived ferrite (Ni,Zn)Fe2O4 ceramics

    NASA Astrophysics Data System (ADS)

    Chen, D. G.; Tang, X. G.; Liu, Q. X.; Jiang, Y. P.; Ma, C. B.; Li, R.

    2013-06-01

    Dielectric spectra and magnetization hysteresis loops were used to investigate the grain size effect with temperature on the electrical and magnetic response of co-precipitation derived spinel (Ni0.5Zn0.5)Fe2O4 (NZFO) ceramics. Remarkable dielectric relaxation phenomena of non-Debye type have been observed in each NZFO ceramics as confirmed by two kinds of Cole-Cole plots of the 1100 °C sintered samples, mainly due to the electron-hopping mechanism between n-type and p-type carriers and interfacial ion effect when applied an increase of temperature. The high and low response of grain and grain-boundary regions were determined by modeling the impedance experimental results on two equivalent RC circuits taking into account grain deep trap states. By employing the modified Arrhenius equation, activation energy values of different sintering temperatures were calculated and analyzed in combination with oxygen vacancy. In addition, the magnetization of various sintering temperature samples is dominated by cation distribution and surface effect in different particle ranges.

  11. Flexion Relaxation Ratio Not Responsive to Acutely Induced Low Back Pain from a Delayed Onset Muscle Soreness Protocol

    PubMed Central

    Horn, Maggie E.; Bishop, Mark D.

    2013-01-01

    Background. The flexion relaxation ratio (FRR) has been suggested as a measure of muscular performance in patients with low back pain (LBP). The purpose of this study was to investigate whether the FRR was responsive to acute LBP produced from a delayed onset muscle soreness (DOMS) protocol. Methods. Fifty-one pain-free volunteers performed DOMS to induce LBP. Current pain intensity, trunk flexion range of motion (ROM), and passive straight leg raise (SLR) were measured at baseline, 24 and 48 hours after DOMS. Participants were categorized into pain groups based on reported current pain intensity. Changes in FRR, trunk flexion ROM, and SLR ROM were examined using two-way repeated measures analysis of variance. Results. Pain group was not found to have a significant effect on FRR (F1,29 = 0.054, P = 0.818), nor were there any two-way interactions for changes in FRR. The pain group had decreased trunk flexion ROM compared to the minimal pain group (F1,38 = 7.21, P = 0.011), but no decreases in SLR ROM (F1,38 = 3.51, P = 0.057) over time. Interpretation. There were no differences in FRR based on reported pain intensity of LBP from a DOMS protocol. The responsiveness of FRR might be limited in patients with acute onset LBP of muscular origin. PMID:27335879

  12. 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

  13. The response of the rabbit subsynovial connective tissue to a stress-relaxation test.

    PubMed

    Morizaki, Yutaka; Vanhees, Matthias; Thoreson, Andrew R; Larson, Dirk; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C

    2012-03-01

    The subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in the etiology of carpal tunnel syndrome (CTS), yet the material properties of the SSCT remain unclear. Thus, we investigated the mechanical response of the SSCT in a rabbit model. Twenty-four rabbit cadaver paws were used for mechanical testing; two paws were used for scanning electron microscopy (SEM) imaging. After testing normal tendon excursion, the divided third digit flexor digitorum superficialis (FDS) tendon was pulled to displacements of 2, 3.5, 5, or 8 mm, maintained at that position until force decay, and then the process was repeated. Normal excursion of the FDS averaged 4.8 mm. The ratio of the second peak force to the first peak force in the 2 mm group was 0.98 (SD = 0.16), which was significantly higher than the other groups (3.5 mm: 0.74, 5 mm, 0.63, and 8 mm: 0.59; p < 0.05). SEM showed ruptured fibrils in the displaced specimen. The declining force ratio with displacements >2 mm suggests damage to the SSCT within the physiological tendon excursion. These data may be useful in understanding SSCT mechanics in CTS, which is associated with SSCT fibrosis. PMID:21898581

  14. Comparison of the Ca2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908.

    PubMed

    Tanaka, Y; Imai, T; Igarashi, T; Takayanagi, K; Otsuka, K; Yamaki, F; Tanaka, H; Shigenobu, K

    2000-08-01

    Noradrenaline (NA) produces sustained contractions in conduit arteries such as aorta isolated from various animal species. In guinea-pig aorta, NA-produced sustained contraction is largely dependent upon the influx of extracellular Ca2+, but is refractory to the treatment with organic Ca2+ entry blockers. In the present study, we attempted to characterize pharmacologically the Ca2+ entry channel responsible for NA-produced sustained contraction of guinea-pig aorta using SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi dazole) and LOE 908 ((R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2- (2,3,4-trimethoxyphenyl)ethyl]-acetamide), both of which block voltage-independent Ca2+ channels. The effects of SK&F 96365 and LOE 908 on NA-produced contraction were compared with those on extracellular Ca2+-dependent contractile and endothelium-dependent relaxant responses to thapsigargin (TSG), an inhibitor of Ca2+-pump Ca2+-ATPase. NA (3x10(-6) M)-produced sustained contraction of guinea-pig aorta without endothelium exhibited a strong dependency on the extracellular Ca2+. Nicardipine (10(-7) M), diltiazem (10(-5) M) and verapamil (10(-5) M) did not show any appreciable inhibitory effects on NA-produced sustained contraction. SK&F 96365 concentration-dependently (10(-6)-10(-4) M) attenuated the NA-produced sustained contraction whereas LOE 908 did not affect it at concentrations up to 10(-4) M. Similarly, extracellular Ca2+-dependent contraction of guinea-pig aorta without endothelium in response to TSG was also diminished by SK&F 96365 but was unaffected by LOE 908. In fura-PE3-loaded vascular preparations, SK&F 96365 decreased both cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension elevated by NA and TSG. Both SK&F 96365 and LOE 908 did not affect an endothelium-dependent relaxation of guinea-pig aorta in response to TSG. These findings suggest that in guinea-pig aortic smooth muscle cells, NA activates Ca2+ influx across

  15. 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. PMID:26825543

  16. Relaxation System

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Environ Corporation's relaxation system is built around a body lounge, a kind of super easy chair that incorporates sensory devices. Computer controlled enclosure provides filtered ionized air to create a feeling of invigoration, enhanced by mood changing aromas. Occupant is also surrounded by multidimensional audio and the lighting is programmed to change colors, patterns, and intensity periodically. These and other sensory stimulators are designed to provide an environment in which the learning process is stimulated, because research has proven that while an individual is in a deep state of relaxation, the mind is more receptive to new information.

  17. Three Gaseous Neurotransmitters, Nitric oxide, Carbon Monoxide, and Hydrogen Sulfide, Are Involved in the Neurogenic Relaxation Responses of the Porcine Internal Anal Sphincter

    PubMed Central

    Folasire, Oladayo; Mills, Kylie A; Sellers, Donna J; Chess-Williams, Russ

    2016-01-01

    Background/Aims The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Methods Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Results Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45% at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with α,β-methylene-ATP (10 μM). In the presence of guanethidine, atropine, and α,β-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 μM), the vasoactive intestinal polypeptide receptor antagonist, [d-p-Cl-Phe6,Leu17]-vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by Nω-nitro-L-arginine (L-NNA; 100 μM), an inhibitor of nitric oxide synthesis (40–50% reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20–40% reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15–20% reduction). Conclusions Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide

  18. Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium

    PubMed Central

    Raffai, Gábor; Kim, Byungkuk; Park, Sanga; Khang, Gilson; Lee, Dongwon; Vanhoutte, Paul M

    2014-01-01

    Background and purpose Cinnamaldehyde, a major component of cinnamon, induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects, but its short half-life limits its clinical use. The present experiments were designed to compare the acute relaxing properties of cinnamaldehyde with those of self-assembling polymer micelles either loaded with cinnamaldehyde or consisting of a polymeric prodrug [poly(cinnamaldehyde)] that incorporates the compound in its backbone. Methods Rings of porcine coronary arteries were contracted with the thromboxane A2 receptor agonist U46619 or 40 mM KCl, and changes in isometric tension were recorded. Results Cinnamaldehyde induced concentration-dependent but endothelium-independent, nitric oxide synthase (NOS)-independent, cyclooxygenase-independent, soluble guanylyl cyclase (sGC)-independent, calcium-activated potassium-independent, and TRPA1 channel-independent relaxations. Cinnamaldehyde also inhibited the contractions induced by 40 mM KCl Ca2+ reintroduction in 40 mM KCl Ca2+-free solution or by the Ca2+ channel opener Bay K8644. Cinnamaldehyde-loaded control micelles induced complete, partly endothelium-dependent relaxations sensitive to catalase and inhibitors of NOS or sGC, but not cyclooxygenase or TRPA1, channels. Cinnamaldehyde-loaded micelles also inhibited contractions induced by 40 mM KCl Ca2+ reintroduction or Bay K8644. Poly(cinnamaldehyde) micelles induced only partial, endothelium-dependent relaxations that were reduced by inhibitors of NOS or sGC and by catalase and the antioxidant tiron, but not by indomethacin or TRPA1 channel blockers. Conclusion The present findings demonstrate that cinnamaldehyde-loaded and poly(cinnamaldehyde) micelles possess vasodilator properties, but that the mechanism underlying the relaxation that they cause differs from that of cinnamaldehyde, and thus could be used both to relieve coronary vasospasm and for therapeutic drug delivery. PMID:24904214

  19. A High Frequency Response Relaxed Eddy Accumulation Flux Measurement System for Sampling Short-Lived Biogenic Volatile Organic Compounds

    EPA Science Inventory

    A second-generation relaxed eddy accumulation system was built and tested with the capability to measure vertical biogenic volatile organic compound (VOC) fluxes at levels as low as 10 µg C m−2 hr−1. The system features a continuous, integrated gas-phase ozo...

  20. The Effect of Tempol Administration on the Aortic Contractile Responses in Rat Preeclampsia Model

    PubMed Central

    Talebianpoor, Mohammad Sharif; Mirkhani, Hossein

    2012-01-01

    It is reported that reactive oxygen species production has a critical role in the manifestations and complications of preeclampsia. In the present study, the effect of tempol on the response changes of aortic rings of preeclamptic rats has been studied. Preeclamptic rats (induced by L-NAME) were treated with three different oral doses of tempol (20, 60 and 180 mg/kg/day) from the Day 10 of gestation. Systolic blood pressure, plasma malondialdehyde and 8-isoprostane and the vascular effects of phenylephrine, calcium, acetylcholine and diazoxide were the studied parameters. L-NAME administration resulted in hypertension, proteinuria, increased oxidative stress markers, increased vascular sensitivity to phenylephrine and decreased sensitivity to acetylcholine in pregnant rats. No significant changes in response to calcium and diazoxide were observed. Tempol at doses of 20 and 60 mg/kg/day significantly reversed these changes but at a high dose (180 mg/kg/day), it had no significant effect and in some cases intensified the effect. These results revealed that in the experimental preeclampsia, the sensitivity of rat aorta to alpha- adrenergic receptor agonists was increased and its endothelium-dependent relaxation was decreased. Tempol at lower used doses reduced the blood pressure and oxidative stress and restored the normal responsiveness of vascular tissue in preeclamptic rats. PMID:22988523

  1. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    PubMed

    Seo, K K; Lee, M Y; Lim, S W; Kim, S C

    1999-02-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  2. Impaired vasodilator response to organic nitrates in isolated basilar arteries

    PubMed Central

    Martens, Dorothee; Kojda, Georg

    2001-01-01

    The differential responsiveness of various sections and regions in the vascular system to the vasodilator activity of organic nitrates is important for the beneficial antiischaemic effects of these drugs. In this study we examined the vasodilator activity of organic nitrates in cerebral arteries, where vasodilation causes substantial nitrate induced headache. Isolated porcine basilar and coronary arteries were subjected to increasing concentrations of glyceryl trinitrate (GTN), isosorbide-5-nitrate (ISMN) and pentaerythritol tetranitrate (PETN). S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and endothelium-dependent vasodilation was investigated for comparison purpose. The vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.33±0.1, n=8), ISMN (1.61±0.07, n=7) and PETN (>10 μM, n=7) in basilar arteries was more than 100 fold lower than that of GTN (6.52±0.06, n=12), ISMN (3.66±0.08, n=10) and PETN (6.3±0.13, n=8) observed in coronary arteries. In striking contrast, the vasodilator potency of SNAP (halfmaximal effective concentration in −logM) was almost similar in basilar (7.76±0.05, n=7) and coronary arteries (7.59±0.05, n=9). Likewise, no difference in endothelium dependent relaxation was observed. Denudation of the endothelium resulted in a small increase of the vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.84±0.09, n=7, P<0.03) in basilar arteries and similar results were obtained in the presence of the NO-synthase inhibitor Nω-nitro-L-arginine (4.59±0.05, n=9, P<0.03). These results suggest that cerebral conductance blood vessels such as porcine basilar arteries seems to have a reduced expression and/or activity of certain cellular enzymatic electron transport systems such as cytochrome P450 enzymes, which are necessary to bioconvert organic nitrates to NO. PMID:11156558

  3. Simulation of DNA Supercoil Relaxation.

    PubMed

    Ivenso, Ikenna D; Lillian, Todd D

    2016-05-24

    Several recent single-molecule experiments observe the response of supercoiled DNA to nicking endonucleases and topoisomerases. Typically in these experiments, indirect measurements of supercoil relaxation are obtained by observing the motion of a large micron-sized bead. The bead, which also serves to manipulate DNA, experiences significant drag and thereby obscures supercoil dynamics. Here we employ our discrete wormlike chain model to bypass experimental limitations and simulate the dynamic response of supercoiled DNA to a single strand nick. From our simulations, we make three major observations. First, extension is a poor dynamic measure of supercoil relaxation; in fact, the linking number relaxes so fast that it cannot have much impact on extension. Second, the rate of linking number relaxation depends upon its initial partitioning into twist and writhe as determined by tension. Third, the extensional response strongly depends upon the initial position of plectonemes. PMID:27224483

  4. Different β-adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels

    PubMed Central

    Flacco, N; Segura, V; Perez-Aso, M; Estrada, S; Seller, JF; Jiménez-Altayó, F; Noguera, MA; D'Ocon, P; Vila, E; Ivorra, MD

    2013-01-01

    Background and Purpose To analyse the relative contribution of β1-, β2- and β3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while β2- and β3-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (β3-agonist) relaxed aorta, but not MRA. Conclusion and Implication Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels. PMID:23373597

  5. Glycation does not modify bovine serum albumin (BSA)-induced reduction of rat aortic relaxation: The response to glycated and nonglycated BSA is lost in metabolic syndrome

    PubMed Central

    Rubio-Ruiz, Maria Esther; Díaz-Díaz, Eulises; Cárdenas-León, Mario; Argüelles-Medina, Rabindranath; Sánchez-Canales, Patricia; Larrea-Gallo, Fernando; Soria-Castro, Elizabeth; Guarner-Lans, Verónica

    2008-01-01

    The effects of nonglycated bovine serum albumin (BSA) and advanced glycosylation end products of BSA (AGE-BSA) on vascular responses of control and metabolic syndrome (MS) rats characterized by hypertriglyceridemia, hypertension, hyperinsulinemia, and insulin resistance were studied. Albumin and in vitro prepared AGE-BSA have vascular effects; however, recent studies indicate that some effects of in vitro prepared AGEs are due to the conditions in which they were generated. We produced AGEs by incubating glucose with BSA for 60 days under sterile conditions in darkness and at 37°C. To develop MS rats, male Wistar animals were given 30% sucrose in drinking water since weanling. Six month old animals were used. Blood pressure, insulin, triglycerides, and serum albumin were increased in MS rats. Contraction of aortic rings elicited with norepinephrine was stronger. There were no effects of nonglycated BSA or AGE-BSA on contractions in control or MS rats; however, both groups responded to L-NAME, an inhibitor of nitric oxide synthesis. Arterial relaxation induced using acetylcholine was smaller in MS rats. Nonglycated BSA and AGE-BSA significantly diminished relaxation in a 35% in the control group but the decrease was similar when using nonglycated BSA and AGE-BSA. This decrease was not present in the MS rats and was not due to increased RAGEs or altered biochemical characteristics of BSA. In conclusion, both BSA and AGE-BSA inhibit vascular relaxation in control artic rings. In MS rats the effect is lost possibly due to alterations in endothelial cells that are a consequence of the illness. PMID:18458031

  6. Breathing and Relaxation

    MedlinePlus

    ... Top Doctors in the Nation Departments & Divisions Home Health Insights Stress & Relaxation Breathing and Relaxation Breathing and Relaxation Make ... Management Assess Your Stress Coping Strategies Identifying ... & Programs Health Insights Doctors & Departments Research & Science Education & Training Make ...

  7. Dielectric relaxation and magnetodielectric response in DyMn0.5Cr0.5O3

    NASA Astrophysics Data System (ADS)

    Yuan, B.; Yang, J.; Zuo, X. Z.; Kan, X. C.; Zu, L.; Zhu, X. B.; Dai, J. M.; Song, W. H.; Sun, Y. P.

    2015-09-01

    We investigate the structural, magnetic, and magnetodielectric properties of DyMn0.5Cr0.5O3. The sample can be indexed with an orthorhombic phase with B site disordered space group Pbnm. The valence state of both Mn and Cr ions are suggested to be +3 based on the results of x-ray photoelectron spectroscopy. Two thermally excited dielectric relaxation at temperatures TN2 < T< 300 K and large magnetodielectric effect (MDC = 20%-30%) due to the disordered arrangement of Mn3+/Cr3+ ions associated with electron hopping between them are observed. The absence of any noticeable magnetoresistance effect (MR < 0.5%) demonstrates that the observed magnetodielectric effect is an intrinsic behavior. These results suggest that DyMn0.5Cr0.5O3 is a magnetodielectric compound, whose dielectric properties are dependence of the applied magnetic field, which exhibits such effects near room temperature and holds great promise for future device applications.

  8. Relaxation Assessment with Varied Structured Milieu (RELAX).

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1983-01-01

    Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

  9. Hydrogen peroxide induced relaxation in porcine pulmonary arteries in vitro is mediated by EDRF and cyclic GMP

    SciTech Connect

    Zellers, T.; McCormick, J. )

    1991-03-15

    Xanthine and xanthine oxidase induced relaxations in porcine pulmonary arteries in vitro are augmented in the presence of the endothelium and abolished by catalase, implicating hydrogen peroxide as an endothelium-dependent effector. To determine the mechanism whereby H{sub 2}O{sub 2} causes relaxations, isolated rings of fifth order porcine pulmonary artery, with (E{sup +}) and without (E{sup {minus}}) endothelium, were suspended in organ baths filled with buffer, and isometric tension was recorded. Hydrogen peroxide caused concentration-dependent, endothelium-augmented relaxations which were abolished by catalase and hydroquinone and reversed by L-nitroarginine and methylene blue. Prostacyclin (PGI{sub 2}) levels, measured after a two minute exposure to H{sub 2}O{sub 2} in rings with endothelium were comparable to controls. This concentration of PGI{sub 2} does not cause relaxations in these rings. These data suggest that H{sub 2}O{sub 2} stimulates the release of an EDRF, causing relaxations mediated by cyclic GMP, which is independent of prostacyclin.

  10. [Pulmonary vasoconstrictor responses].

    PubMed

    Onodera, S

    1992-12-01

    from that of isoproterenol. The importance of the K+ channel of vascular smooth muscle and also the endothelium in hypoxic pulmonary vasoconstriction were stressed. In isolated pulmonary artery segments of the monocrotaline-treated rat, the augmentation of sensitivity of the vascular smooth muscle to Ca2+ preceded the occurrence of pulmonary hypertension. Similarly, hyperreactivity to KCl and serotonin was also observed. It was clarified that the hyperreactivity induced by monocrotaline is modified by endothelium-dependent relaxation. Extensive cellular and molecular biological investigations are essential for further progress in this field. PMID:1363972

  11. Characterization of relaxant mechanism of H2 S in mouse corpus cavernosum.

    PubMed

    Aydinoglu, Fatma; Ogulener, Nuran

    2016-04-01

    The aim of this study was to investigate the mechanism of H2 S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6) × 10(-3) mol/L) and exogenous H2 S (NaHS; 10(-6) to 10(-3) mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2 S diminished in endothelium-denuded tissues. N(ω) -nitro-l-arginine (l-NA; 10(-4) mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4) mol/L), a guanylyl cyclase inhibitor, increased the H2 S-induced relaxation. Zaprinast (5 × 10(-6) mol/L) and sildenafil (10(-6) mol/L), phosphodiesterase inhibitors, inhibited H2 S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5 × 10(-5) mol/L) and SQ22536 (10(-4) mol/L) reduced relaxation to H2 S. Also, H2 S-induced relaxation was reduced by KCl (50 mmol/L), 4-aminopyridine (10(-3) mol/L), a Kv inhibitor, glibenclamide (10(-5) mol/L), a KATP inhibitor or barium chloride (10(-5) mol/L), a KIR inhibitor. However, H2 S-induced relaxation was not influenced by apamin (10(-6) mol/L), a SKC a (2+) inhibitor, charybdotoxin (10(-7) mol/L), an IKC a (2+) and BKC a (2+) inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6) mol/L), an L-type calcium channel blocker and atropine (10(-6) mol/L), a muscarinic receptor blocker, inhibited H2 S-induced relaxation. However, H2 S-induced relaxation was not influenced by ouabain (10(-4) mol/L), a Na(+) /K(+) -ATPase inhibitor. This study suggests that H2 S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2 S may cause endothelium-independent relaxations via activation of K channels (KATP channel, KV channels, KIR channels), L-type voltage-gated Ca(2+) channels, adenylyl cyclase

  12. Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries.

    PubMed

    Gauthier, Kathryn M; Goldman, Daniel H; Aggarwal, Nitin T; Chawengsub, Yuttana; Falck, J R; Campbell, William B

    2011-03-01

    immunoblot analysis and RT-PCR of the aorta and mesenteric arteries demonstrated protein and mRNA expression of leukocyte-type 12/15-LO. Thus, in mouse resistance arteries, 12/15-LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA. PMID:21193584

  13. Heart rate and autonomic response to stress after experimental induction of worry versus relaxation in healthy, high-worry, and generalized anxiety disorder individuals.

    PubMed

    Fisher, Aaron J; Newman, Michelle G

    2013-04-01

    Generalized anxiety disorder (GAD) is the most commonly occurring anxiety disorder and has been related to cardiovascular morbidity such as cardiac ischemia, sudden cardiac death, and myocardial infarction. Both GAD and its cardinal symptom - worry - have been shown to promote muted physiological reactivity in response to laboratory and ecological stressors. Importantly, no study to date has examined the concurrent and relative contributions of trait and state worry within healthy controls, (non-clinical) high trait-worry controls, and GAD participants. The present study examined heart rate (HR), respiratory sinus arrhythmia (RSA), and salivary alpha-amylase (sAA) responses to laboratory stress during and following the experimental induction of worry versus relaxation in healthy controls (n=42), high trait worriers (n=33) and participants with GAD (n=76). All groups exhibited increased HR and decreased RSA in response to the stressor, with no differences by condition. Baseline sAA significantly moderated HR and RSA reactivity, such that higher sAA predicted greater increases in HR and decreases in RSA. There was a significant group by baseline sAA interaction such that in GAD, higher baseline sAA predicted decreased change in sAA during stress, whereas higher baseline sAA predicted greater sAA change in healthy controls. High-worry controls fell non-significantly between these groups. The present study provides additional evidence for the effect of worry on diminished HR stress response and points to possible suppression of adrenergic sympathetic stress responses in GAD. PMID:23384513

  14. Protective Effect and Mechanism of Total Flavones from Rhododendron simsii Planch on Endothelium-Dependent Dilatation and Hyperpolarization in Cerebral Ischemia-Reperfusion and Correlation to Hydrogen Sulphide Release in Rats

    PubMed Central

    Han, Jun; He, Guo-Wei; Chen, Zhi-Wu

    2014-01-01

    We for the first time investigated the effect and mechanism of the total flavones of Rhododendron simsii Planch (TFR), a widely-used Chinese herb for a thousand years, on vasodilatation and hyperpolarization in middle cerebral artery (MCA) of rats subject to global cerebral ischemia-reperfusion (CIR). TFR (11~2700 mg/L) evoked dose-dependent vasodilation and hyperpolarization in MCA of both sham and CIR that were partially inhibited by 30 μM N-nitro-L-arginine-methyl-ester and 10 μM indomethacin and further attenuated by endogenous H2S synthese-CSE inhibitor PPG (100 μM) or Ca2+-activated potassium channel (Kca) inhibitor TEA (1 mM). In whole-cell patch clamp recording, TFR remarkably enhanced the outward current that was inhibited by TEA. CIR increased CSE mRNA expression and the contents of H2S that were further increased by TFR. We conclude that, in MCA of CIR rats, TFR induces non-NO and non-PGI2-mediated effects of vasodilatation and hyperpolarization involving Kca and increases CSE mRNA expression level in endothelial cells and H2S content in the cerebrum. These findings suggest that the response induced by TFR is potentially related to endothelium-derived hyperpolarizing factor mediated by the endogenous H2S and promote the use of TFR in protection of brain from ischemia-reperfusion injury. PMID:25050128

  15. Impedance response and dielectric relaxation in co-precipitation derived ferrite (Ni,Zn)Fe{sub 2}O{sub 4} ceramics

    SciTech Connect

    Chen, D. G.; Tang, X. G.; Liu, Q. X.; Jiang, Y. P.; Ma, C. B.; Li, R.

    2013-06-07

    Dielectric spectra and magnetization hysteresis loops were used to investigate the grain size effect with temperature on the electrical and magnetic response of co-precipitation derived spinel (Ni{sub 0.5}Zn{sub 0.5})Fe{sub 2}O{sub 4} (NZFO) ceramics. Remarkable dielectric relaxation phenomena of non-Debye type have been observed in each NZFO ceramics as confirmed by two kinds of Cole-Cole plots of the 1100 Degree-Sign C sintered samples, mainly due to the electron-hopping mechanism between n-type and p-type carriers and interfacial ion effect when applied an increase of temperature. The high and low response of grain and grain-boundary regions were determined by modeling the impedance experimental results on two equivalent RC circuits taking into account grain deep trap states. By employing the modified Arrhenius equation, activation energy values of different sintering temperatures were calculated and analyzed in combination with oxygen vacancy. In addition, the magnetization of various sintering temperature samples is dominated by cation distribution and surface effect in different particle ranges.

  16. Magnetic resonance diffusion and relaxation characterization of water in the unfrozen vein network in polycrystalline ice and its response to microbial metabolic products

    NASA Astrophysics Data System (ADS)

    Brown, Jennifer R.; Brox, Timothy I.; Vogt, Sarah J.; Seymour, Joseph D.; Skidmore, Mark L.; Codd, Sarah L.

    2012-12-01

    Polycrystalline ice, as found in glaciers and the ice sheets of Antarctica, is a low porosity porous media consisting of a complicated and dynamic pore structure of liquid-filled intercrystalline veins within a solid ice matrix. In this work, Nuclear Magnetic Resonance measurements of relaxation rates and molecular diffusion, useful for probing pore structure and transport dynamics in porous systems, were used to physically characterize the unfrozen vein network structure in ice and its response to the presence of metabolic products produced by V3519-10, a cold tolerant microorganism isolated from the Vostok ice core. Recent research has found microorganisms that can remain viable and even metabolically active within icy environments at sub-zero temperatures. One potential mechanism of survival for V3519-10 is secretion of an extracellular ice binding protein that binds to the prism face of ice crystals and inhibits ice recrystallization, a coarsening process resulting in crystal growth with ice aging. Understanding the impact of ice binding activity on the bulk vein network structure in ice is important to modeling of frozen geophysical systems and in development of ice interacting proteins for biotechnology applications, such as cryopreservation of cell lines, and manufacturing processes in food sciences. Here, we present the first observations of recrystallization inhibition in low porosity ice containing V3519-10 extracellular protein extract as measured with Nuclear Magnetic Resonance and Magnetic Resonance Imaging.

  17. Psychophysiological Effects of Progressive Relaxation in Anxiety Neurotic Patients and of Progressive Relaxation and Alpha Feedback in Nonpatients.

    ERIC Educational Resources Information Center

    Lehrer, Paul M.

    1978-01-01

    Compared physiological effects of progressive relaxation, alpha feedback, and a no-treatment condition. Nonpatients showed more psychophysiological habituation than patients in response to hearing very loud tones and to reaction time tasks. Patients showed greater physiological response to relaxation than nonpatients. After relaxation, autonomic…

  18. The Endothelium-Dependent Nitric Oxide-cGMP Pathway.

    PubMed

    Mónica, F Z; Bian, K; Murad, F

    2016-01-01

    Nitric oxide (NO)-cyclic 3'-5' guanosine monophosphate (cGMP) signaling plays a critical role on smooth muscle tone, platelet activity, cardiac contractility, renal function and fluid balance, and cell growth. Studies of the 1990s established endothelium dysfunction as one of the major causes of cardiovascular diseases. Therapeutic strategies that benefit NO bioavailability have been applied in clinical medicine extensively. Basic and clinical studies of cGMP regulation through activation of soluble guanylyl cyclase (sGC) or inhibition of cyclic nucleotide phosphodiesterase type 5 (PDE5) have resulted in effective therapies for pulmonary hypertension, erectile dysfunction, and more recently benign prostatic hyperplasia. This section reviews (1) how endothelial dysfunction and NO deficiency lead to cardiovascular diseases, (2) how soluble cGMP regulation leads to beneficial effects on disorders of the circulation system, and (3) the epigenetic regulation of NO-sGC pathway components in the cardiovascular system. In conclusion, the discovery of the NO-cGMP pathway revolutionized the comprehension of pathophysiological mechanisms involved in cardiovascular and other diseases. However, considering the expression "from bench to bedside" the therapeutic alternatives targeting NO-cGMP did not immediately follow the marked biochemical and pathophysiological revolution. Some therapeutic options have been effective and released on the market for pulmonary hypertension and erectile dysfunction such as inhaled NO, PDE5 inhibitors, and recently sGC stimulators. The therapeutic armamentarium for many other disorders is expected in the near future. There are currently numerous active basic and clinical research programs in universities and industries attempting to develop novel therapies for many diseases and medical applications. PMID:27451093

  19. Shoreline relaxation at pocket beaches

    NASA Astrophysics Data System (ADS)

    Turki, Imen; Medina, Raul; Kakeh, Nabil; González, Mauricio

    2015-09-01

    A new physical concept of relaxation time is introduced in this research as the time required for the beach to dissipate its initial perturbation. This concept is investigated using a simple beach-evolution model of shoreline rotation at pocket beaches, based on the assumption that the instantaneous change of the shoreline plan-view shape depends on the long-term equilibrium plan-view shape. The expression of relaxation time is developed function of the energy conditions and the physical characteristics of the beach; it increases at longer beaches having coarse sediments and experiencing low-energy conditions. The relaxation time, calculated by the developed model, is validated by the shoreline observations extracted from video images at two artificially embayed beaches of Barcelona (NW Mediterranean) suffering from perturbations of sand movement and a nourishment project. This finding is promising to estimate the shoreline response and useful to improve our understanding of the dynamic of pocket beaches and their stability.

  20. Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

    PubMed

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-06-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  1. Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

    PubMed Central

    Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

    2015-01-01

    Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that

  2. The relaxation response resiliency program (3RP) in patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis: results from a pilot study.

    PubMed

    Vranceanu, Ana-Maria; Merker, Vanessa L; Plotkin, Scott R; Park, Elyse R

    2014-10-01

    NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3RP) aimed at improving resiliency and increasing satisfaction with life. Patients seen at MGH's Neurofibromatosis Clinic were offered participation if they described difficulties coping to a treating physician. Participants completed measures of life satisfaction, resiliency, stress, mood, lifestyle, pain, post-traumatic growth and mindfulness at baseline and after completing the 3RP program. The intervention had relative feasible enrollment rate (48% rate, 32 out of 67 of patients signing the informed consent form). However, out of the 32 patients who signed the informed consent, only 20 started the study (62.5%) and only 16 completed it (50%), suggesting problems with feasibility. The main reason cited for non-participation was burden of travel to the clinic. The intervention was highly acceptable, as evidenced by an 80% completion rate (16/20). Paired t tests showed significant improvement in resiliency, satisfaction with life, depression, stress, anxiety, mindfulness and post traumatic growth, with effect sizes ranging from 0.73-1.33. There was a trend for significance for improvement in somatization and sleepiness (p = 0.06), with effect sizes of 0.54-0.92 respectively. Statistically nonsignificant improvement was observed in all other measures, with effect sizes small to medium. In sum, the 3RP was found to be relatively feasible, highly acceptable and preliminary efficacious in decreasing symptom burden in this population, supporting the need of a randomized controlled trial. PMID:25022450

  3. Mechanism of rotational relaxation.

    NASA Technical Reports Server (NTRS)

    Polanyi, J. C.; Woodall, K. B.

    1972-01-01

    A model is presented which describes the characteristic pattern of relaxation of a nonthermal rotational distribution of hydrogen halide, peaked initially at high rotational quantum number J, to a thermal distribution without generating a peak at intermediate J. A method for correcting infrared chemiluminiscence data for modest rotational relaxation is also suggested.

  4. TEACHING NEUROMUSCULAR RELAXATION.

    ERIC Educational Resources Information Center

    NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

    THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

  5. Nitrovasodilator-induced relaxation and tolerance development in porcine vena cordis magna: dependence on intact endothelium.

    PubMed Central

    Kojda, G.; Beck, J. K.; Meyer, W.; Noack, E.

    1994-01-01

    1. Isolated segments of porcine vena cordis magna exhibited a reproducible contractile activity upon application of prostaglandin F2 alpha (PGF2 alpha) or KCl, that was independent of the presence of intact endothelium. Substance P (3 nM) elicited strictly endothelium-dependent relaxations amounting to 46.1 +/- 1.4% (n = 206) of contractions induced by 10 microM PGF2 alpha. 2. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a compound that spontaneously liberates nitric oxide, concentration-dependently relaxed PGF2 alpha-precontracted (50 microM) venous segments. Tolerance induction (incubation with 100 microM SNAP for 30 min) within the same segments resulted in a 3 fold attenuation of this effect, which was not further reduced after additional preincubation with glyceryl trinitrate (GTN). Removal of endothelium or the presence of N omega-nitro-L-arginine methylester (L-NAME) significantly improved the potency of SNAP before and after tolerance induction. 3. Concentration-dependent relaxations induced by GTN in non-tolerant veins were similar in the presence and absence of endothelium but much more reduced in tolerant endothelium-denuded (75 fold) compared to intact (20 fold) segments. In contrast, the presence of L-NAME significantly improved GTN-activity solely in non-tolerant veins, which, therefore, also resulted in a more pronounced attenuation of activity due to tolerance induction (100 fold). Preincubation of intact veins with SNAP also reduced GTN-activity but to a lesser extent (10 fold). 4. The more delayed but much longer, and compared to GTN somewhat weaker, acting new nitrovasodilator N-(3-nitrato-pivaloyl)-1-cysteineethylester (SPM 3672) was more potent in denuded than intact non-tolerant venous segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7521258

  6. Relaxation techniques for children and young people.

    PubMed

    Hobbie, C

    1989-01-01

    The relaxation response, relaxation with mental imagery/self-hypnosis, and centering are techniques that can be used by the nurse practitioner in a variety of clinical situations to help children and young people manage stress. These approaches also can be used to treat certain common pediatric problems, such as headaches, enuresis, acute and chronic pain, and habit disorders. The techniques and their appropriate use are described. PMID:2647960

  7. Activation of endothelial and epithelial KCa2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

    PubMed Central

    Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm; Laursen, Britt E; Pilegaard, Hans; Köhler, Ralf; Simonsen, Ulf

    2012-01-01

    BACKGROUND AND PURPOSE Small (KCa2) and intermediate (KCa3.1) conductance calcium-activated potassium channels (KCa) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of KCa2.3 and KCa3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries. EXPERIMENTAL APPROACH Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. KCa2 and KCa3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques. RESULTS While KCa2.3 expression was similar, KCa3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive KCa2.3 and KCa3.1 proteins were found in both endothelium and epithelium. KCa currents were present in HSAEpi cells and sensitive to the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the KCa2.3/ KCa3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the KCa2 channel blocker apamin, while the KCa3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01–1 µM). CONCLUSIONS AND IMPLICATIONS KCa2.3 and KCa3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. KCa2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease. PMID:22506557

  8. Spin relaxation in metallic ferromagnets

    NASA Astrophysics Data System (ADS)

    Berger, L.

    2011-02-01

    The Elliott theory of spin relaxation in metals and semiconductors is extended to metallic ferromagnets. Our treatment is based on the two-current model of Fert, Campbell, and Jaoul. The d→s electron-scattering process involved in spin relaxation is the inverse of the s→d process responsible for the anisotropic magnetoresistance (AMR). As a result, spin-relaxation rate 1/τsr and AMR Δρ are given by similar formulas, and are in a constant ratio if scattering is by solute atoms. Our treatment applies to nickel- and cobalt-based alloys which do not have spin-up 3d states at the Fermi level. This category includes many of the technologically important magnetic materials. And we show how to modify the theory to apply it to bcc iron-based alloys. We also treat the case of Permalloy Ni80Fe20 at finite temperature or in thin-film form, where several kinds of scatterers exist. Predicted values of 1/τsr and Δρ are plotted versus resistivity of the sample. These predictions are compared to values of 1/τsr and Δρ derived from ferromagnetic-resonance and AMR experiments in Permalloy.

  9. Shear Relaxations of Confined Liquids.

    NASA Astrophysics Data System (ADS)

    Carson, George Amos, Jr.

    Ultrathin (<40 A) films of octamethylcyclotetrasiloxane (OMCTS), hexadecane, and dodecane were subjected to linear and non-linear oscillatory shear between flat plates. Shearing frequencies of 0.1 to 800 s^{-1} were applied at pressures from zero to 0.8 MPa using a surface rheometer only recently developed. In most cases the plates were atomically smooth mica surfaces; the role of surface interactions was examined by replacing these with alkyl chain monolayers. OMCTS and hexadecane were examined at a temperature about 5 Celsius degrees above their melting points and tended to solidify. Newtonian plateaus having enormous viscosities were observed at low shear rates. The onset of shear thinning implied relaxation times of about 0.1 s in the linear structure of the confined liquids. Large activation volumes (~80 nm ^3) suggested that shear involved large-scale collective motion. Dodecane was studied at a much higher temperature relative to its melting point and showed no signs of impending solidification though it exhibited well-defined regions of Newtonian response and power law shear thinning. When treated with molecular sieves before use, dodecane had relaxation times which were short (0.02 s) compared to hexadecane, but still exhibited large-scale collective motion. When treated with silica gel, an unexplained long -time relaxation (10 s) was seen in the Newtonian viscosity of dodecane. The relaxation time of the linear structure, 0.005 s was very small, and the storage modulus was unresolvable. The small activation volume (7nm^3) indicated a much lower level of collective motion. The activation volume remained small when dodecane was confined between tightly bound, low energy, alkyl monolayers. At low strains the storage and loss moduli became very large (>10^4 Pa), probably due to interactions with flaws in the monolayers. Dramatic signs of wall slip were observed at large strains even at low pressures.

  10. Shear relaxations of confined liquids

    SciTech Connect

    Carson, G.A. Jr.

    1992-01-01

    Ultrathin (<40 [angstrom]) films of octamethylcyclotetrasiloxane (OMCTS), hexadecane, and dodecane were subjected to linear and non-linear oscillatory shear between flat plates. Shearing frequencies of 0.1 to 800 s[sup [minus]1] were applied at pressures from zero to 0.8 MPa using a surface rheometer only recently developed. In most cases the plates were atomically smooth mica surfaces; the role of surface interactions was examined by replacing these with alkyl chain monolayers. OMCTS and hexadecane were examined at a temperature about 5 Celcius degrees above their melting points and tended to solidify. Newtonian plateaus having enormous viscosities were observed at low shear rates. The onset of shear thinning implied relaxation times of about 0.1 s in the linear structure of the confined liquids. Large activation volumes ([approximately]80 nm[sup 3]) suggested that shear involved large-scale collective motion. Dodecane was studied at a much higher temperature relative to its melting point and showed no signs of impending solidification though it exhibited well-defined regions of Newtonian response and power law shear thinning. When treated with molecular sieves before use, dodecane had relaxation times which were short (0.02 s) compared to hexadecane, but still exhibited large-scale collective motion. When treated with silica gel, an unexplained long-time relaxation (10 s) was seen in the Newtonian viscosity of dodecane. The relaxation time of the linear structure, 0.005 s was very small, and the storage modulus was unresolvable. The small activation volume (7 nm[sup 3]) indicated a much lower level of collective motion. The activation volume remained small when dodecane was confined between tightly bound, low energy, alkyl monolayers. At low strains the storage and loss moduli became very large (>10[sup 4] Pa), probably due to interactions with flaws in the monolayers. Dramatic signs of wall slip were observed at large strains even at low pressures.

  11. Anomalous C-V response correlated to relaxation processes in TiO2 thin film based-metal-insulator-metal capacitor: Effect of titanium and oxygen defects

    NASA Astrophysics Data System (ADS)

    Kahouli, A.; Marichy, C.; Sylvestre, A.; Pinna, N.

    2015-04-01

    Capacitance-voltage (C-V) and capacitance-frequency (C-f) measurements are performed on atomic layer deposited TiO2 thin films with top and bottom Au and Pt electrodes, respectively, over a large temperature and frequency range. A sharp capacitance peak/discontinuity (C-V anomalous) is observed in the C-V characteristics at various temperatures and voltages. It is demonstrated that this phenomenon is directly associated with oxygen vacancies. The C-V peak irreversibility and dissymmetry at the reversal dc voltage are attributed to difference between the Schottky contacts at the metal/TiO2 interfaces. Dielectric analyses reveal two relaxation processes with degeneration of the activation energy. The low trap level of 0.60-0.65 eV is associated with the first ionized oxygen vacancy at low temperature, while the deep trap level of 1.05 eV is associated to the second ionized oxygen vacancy at high temperature. The DC conductivity of the films exhibits a transition temperature at 200 °C, suggesting a transition from a conduction regime governed by ionized oxygen vacancies to one governed by interstitial Ti3+ ions. Both the C-V anomalous and relaxation processes in TiO2 arise from oxygen vacancies, while the conduction mechanism at high temperature is governed by interstitial titanium ions.

  12. Relaxation phenomenon in composite materials

    NASA Astrophysics Data System (ADS)

    Moznine, R. El.; Blanc, F.; Lieutier, M.; Lefort, A.

    1998-08-01

    Dielectric measurement characteristics such as the dissipation factor, relative permittivity and conductivity as a function of temperature and frequency have been achieved on composite materials based on different epoxy resins filled with alumina inclusions. The analysis of the results show the presence of porosity and inhomogeneity in these materials. The study of the dissipation factor, as a function of temperature at high frequencies, has shown an unexpected absorption phenomenon in materials designed to be utilized as electrical insulators. The identification of the entities responsible for this relaxation shows that the entities result from one of the components of the material. These results can also confirm the inhomogeneity of the materials.

  13. Different vasodilator responses of human arms and legs

    PubMed Central

    Newcomer, Sean C; Leuenberger, Urs A; Hogeman, Cynthia S; Handly, Brian D; Proctor, David N

    2004-01-01

    Forearm vascular responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators have been thoroughly characterized in humans. While the forearm is a well-established experimental model for studying human vascular function, it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements. In the present study we determined whether these responses could be generalized to the leg. Based upon blood pressure differences between the leg and arm during upright posture, we hypothesized that the responsiveness to endothelium-dependent vasodilators would be greater in the forearm than the leg. Brachial and femoral artery blood flow (Q, ultrasound Doppler) at rest and during intra-arterial infusions of endothelium-dependent (acetylcholine and substance P) and -independent (sodium nitroprusside) vasodilators were measured in eight healthy men (22–27 years old). Resting blood flows in the forearm before infusion of acetylcholine, substance P or sodium nitroprusside were 25 ± 4, 30 ± 7 and 29 ± 5 ml min−1, respectively, and in the leg were 370 ± 32, 409 ± 62 and 330 ± 30 ml min−1, respectively. At the highest infusion rate of acetylcholine (16 μg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (1864 ± 476%) than to the leg (569 ± 86%). Similarly, at the highest infusion rate of substance P (125 pg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (911 ± 286%) than to the leg (243 ± 58%). The responses to sodium nitroprusside (1 μg (100 ml tissue)−1 min−1) were also greater (P < 0.05) in the forearm (925 ± 164%) than in the leg (326 ± 65%). These data indicate that vascular responses to both endothelium-dependent and -independent vasodilator agents are blunted in the leg compared to the forearm. PMID:14990681

  14. Suxiao Jiuxin Pill Induces Potent Relaxation and Inhibition on Contraction in Human Artery and the Mechanism

    PubMed Central

    Bai, Xiao-Yan; Zhang, Ping; Yang, Qin; Liu, Xiao-Cheng; Wang, Jun; Tong, Yong-Ling; Xiong, Song-Jin; Liu, Li-Hua; Wang, Lei; He, Guo-Wei

    2014-01-01

    Suxiao Jiuxin Pill, a compound Chinese traditional medicine with main components of tetramethylpyrazine and borneol, is widely used for antiangina treatment in China but its pharmacological effect on human blood vessels is unknown. We investigated the effect and possible mechanism of SJP in the human internal mammary artery (IMA, n = 78) taken from patients undergoing coronary surgery. SJP caused full relaxation in KCl- (99.4 ± 10.5%, n = 6) and U46619- (99.9 ± 5.6%, n = 6) contracted IMA. Pretreatment of IMA with plasma concentrations of SJP (1 mg/mL), calculated from the plasma concentration of its major component borneol, significantly depressed the maximal contraction to KCl (from 35.8 ± 6.0 mN to 12.6 ± 5.6 mN, P = 0.03) and U46619 (from 19.4 ± 2.9 mN to 5.7 ± 2.4 mN, P = 0.007) while SJP at 10 mg/mL abolished the subsequent contraction. Endothelium denudation and inhibition of eNOS significantly altered the SJP-induced relaxation without changes of eNOS expression. We conclude that SJP has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors in human arteries. The vasorelaxation involves both endothelium-dependent and -independent mechanisms. Thus, the effect of SJP on human arteries demonstrated in this study may prove to be particularly important in vasorelaxing therapy in cardiovascular disease. PMID:24808920

  15. Dielectric relaxation time spectroscopy.

    PubMed

    Paulson, K S; Jouravleva, S; McLeod, C N

    2000-11-01

    A new mathematical method is developed to recover the permittivity relaxation spectrum of living tissue from measurements of the real and imaginary parts of the impedance. Aiming to derive information about electrical properties of living tissue without the prior selection of any impedance model, the procedure calculates the relaxation time distribution. It provides new characteristic independent parameters: time constants, their distribution, and the amplitudes of the associated dispersion. As the beta-dispersion is the most important in the area of electrical impedance spectroscopy of tissue, the paper gives an estimate of the essential frequency range to cover the whole relaxation spectrum in that area. Results are presented from both simulation and known lumped--constant element circuit. PMID:11077745

  16. RELAX: detecting relaxed selection in a phylogenetic framework.

    PubMed

    Wertheim, Joel O; Murrell, Ben; Smith, Martin D; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2015-03-01

    Relaxation of selective strength, manifested as a reduction in the efficiency or intensity of natural selection, can drive evolutionary innovation and presage lineage extinction or loss of function. Mechanisms through which selection can be relaxed range from the removal of an existing selective constraint to a reduction in effective population size. Standard methods for estimating the strength and extent of purifying or positive selection from molecular sequence data are not suitable for detecting relaxed selection, because they lack power and can mistake an increase in the intensity of positive selection for relaxation of both purifying and positive selection. Here, we present a general hypothesis testing framework (RELAX) for detecting relaxed selection in a codon-based phylogenetic framework. Given two subsets of branches in a phylogeny, RELAX can determine whether selective strength was relaxed or intensified in one of these subsets relative to the other. We establish the validity of our test via simulations and show that it can distinguish between increased positive selection and a relaxation of selective strength. We also demonstrate the power of RELAX in a variety of biological scenarios where relaxation of selection has been hypothesized or demonstrated previously. We find that obligate and facultative γ-proteobacteria endosymbionts of insects are under relaxed selection compared with their free-living relatives and obligate endosymbionts are under relaxed selection compared with facultative endosymbionts. Selective strength is also relaxed in asexual Daphnia pulex lineages, compared with sexual lineages. Endogenous, nonfunctional, bornavirus-like elements are found to be under relaxed selection compared with exogenous Borna viruses. Finally, selection on the short-wavelength sensitive, SWS1, opsin genes in echolocating and nonecholocating bats is relaxed only in lineages in which this gene underwent pseudogenization; however, selection on the functional

  17. Relaxation techniques for stress

    MedlinePlus

    ... Know. February 2013. Available at: nccih.nih.gov/health/stress/relaxation.htm . Accessed September 21, 2015. National Center ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Stress Browse the Encyclopedia A.D.A.M., Inc. ...

  18. Dielectric relaxation and magnetodielectric response in DyMn{sub 0.5}Cr{sub 0.5}O{sub 3}

    SciTech Connect

    Yuan, B.; Yang, J. Zuo, X. Z.; Zhu, X. B.; Dai, J. M.; Song, W. H.; Kan, X. C.; Zu, L.; Sun, Y. P.

    2015-09-28

    We investigate the structural, magnetic, and magnetodielectric properties of DyMn{sub 0.5}Cr{sub 0.5}O{sub 3}. The sample can be indexed with an orthorhombic phase with B site disordered space group Pbnm. The valence state of both Mn and Cr ions are suggested to be +3 based on the results of x-ray photoelectron spectroscopy. Two thermally excited dielectric relaxation at temperatures T{sub N2} < T< 300 K and large magnetodielectric effect (MDC = 20%–30%) due to the disordered arrangement of Mn{sup 3+}/Cr{sup 3+} ions associated with electron hopping between them are observed. The absence of any noticeable magnetoresistance effect (MR < 0.5%) demonstrates that the observed magnetodielectric effect is an intrinsic behavior. These results suggest that DyMn{sub 0.5}Cr{sub 0.5}O{sub 3} is a magnetodielectric compound, whose dielectric properties are dependence of the applied magnetic field, which exhibits such effects near room temperature and holds great promise for future device applications.

  19. Collection Development: Relaxation & Meditation, September 1, 2010

    ERIC Educational Resources Information Center

    Lettus, Dodi

    2010-01-01

    One of the first books to document the relationship between stress and physical and emotional health was "The Relaxation Response" by Herbert Benson, M.D., with Miriam Z. Klipper. Originally published in 1975, the book grew out of Benson's observations as a cardiologist and his research as a fellow at Harvard Medical School. Benson's study of…

  20. The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces Ca2+ release in rat mesenteric artery endothelial cells

    PubMed Central

    AlSuleimani, Y M; Hiley, C R

    2015-01-01

    Background and Purpose Lysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca2+. Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca2+ responses in endothelial cells isolated from the artery. Experimental Approach Vascular responses were studied using wire myographs. Single-cell fluorescence imaging was performed using a MetaFluor system. Hypotensive effects of LPI were assessed using a Biopac system. Key Results In isolated arteries, LPI-induced vasorelaxation was concentration- and endothelium-dependent and inhibited by CID 16020046, a GPR55 antagonist. The CB1 receptor antagonist AM 251 had no effect, whereas rimonabant and O-1918 significantly potentiated LPI responses. Vasorelaxation was reduced by charybdotoxin and iberiotoxin, alone or combined. LPI decreased systemic arterial pressure. GPR55 is expressed in rat mesenteric artery. LPI caused biphasic elevations of endothelial cell intracellular Ca2+. Pretreatment with thapsigargin or 2-aminoethoxydiphenyl borate abolished both phases. The PLC inhibitor U73122 attenuated the initial phase and enhanced the second phase, whereas the Rho-associated kinase inhibitor Y-27632 abolished the late phase but not the early phase. Conclusions and Implications LPI is an endothelium-dependent vasodilator in the rat small mesenteric artery and a hypotensive agent. The vascular response involves activation of Ca2+-sensitive K+ channels and is not mediated by CB1 receptors, but unexpectedly enhanced by antagonists of the ‘endothelial anandamide’ receptor. In endothelial cells, LPI utilizes PLC-IP3 and perhaps ROCK-RhoA pathways to elevate intracellular Ca2+. Overall, these findings support an endothelial site of action for LPI and suggest a possible role for GPR55 in vasculature. PMID:25652040

  1. Hair Dye and Hair Relaxers

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Hair Dye and Hair Relaxers Share Tweet Linkedin Pin it More sharing ... products. If you have a bad reaction to hair dyes and relaxers, you should: Stop using the ...

  2. Long-Term Psychosomatic Effects of Biofeedback vs. Relaxation Training.

    ERIC Educational Resources Information Center

    Nowlis, David P.; Borzone, Ximena C.

    Differences were compared in the short-term and long-term responses of subjects with headache, insomnia, or hypertension to biofeedback training, relaxation, or a combination of both. Headache sufferers, insomniacs, and hypertensives were randomly assigned in equal numbers to biofeedback, relaxation training or a record-keeping control. Over 2…

  3. Signal prediction by anticipatory relaxation dynamics

    NASA Astrophysics Data System (ADS)

    Voss, Henning U.

    2016-03-01

    Real-time prediction of signals is a task often encountered in control problems as well as by living systems. Here, a parsimonious prediction approach based on the coupling of a linear relaxation-delay system to a smooth, stationary signal is described. The resulting anticipatory relaxation dynamics (ARD) is a frequency-dependent predictor of future signal values. ARD not only approximately predicts signals on average but can anticipate the occurrence of signal peaks, too. This can be explained by recognizing ARD as an input-output system with negative group delay. It is characterized, including its prediction horizon, by its analytically given frequency response function.

  4. Dielectric Relaxation of Hexadeutero Dimethylsulfoxide

    NASA Astrophysics Data System (ADS)

    Betting, H.; Stockhausen, M.

    1999-11-01

    The dielectric relaxation parameters of the title substance (DMSO-d6) in its pure liquid state are determined from meas-urements up to 72 GHz at 20°C in comparison to protonated DMSO. While the relaxation strengths do not differ, the relax-ation time of DMSO-d 6 is significantly longer (21.3 ps) than that of DMSO (19.5 ps).

  5. Vibrational Relaxation in Several Derivatives of Benzene

    NASA Astrophysics Data System (ADS)

    Linde, Bogumił B. J.; Skrodzka, Ewa B.; Lezhnev, Nikołaj B.

    2012-04-01

    Acoustical spectroscopy at frequencies up to 10 GHz gives the possibility of the investigation of liquid substances, where the relaxation process observed is caused by energy transfer between translational and vibrational degrees of freedom. The compounds presented in this article belong to this group of liquids. The acoustic investigations in the group of benzene derivatives, particularly research of the dependencies of acoustic parameters and the structure of organic liquids, demonstrated some interesting regularities in the group of these compounds in gas and liquid states. In this article, the results of research on five cyclic liquids: bromo-, chloro-, fluoro-, iodo-, and nitrobenzene as well as toluene and aniline are discussed and compared to benzene. The acoustic relaxation observed in all these compounds was found to result from Kneser's processes (vibrational relaxation). Based on investigations reported in this article, as well as by other authors, and taking into account experimental and literature data concerning a great number of compounds, one can draw a conclusion that almost all acoustic relaxation (Kneser-type) processes in liquids can be described using a single relaxation time. It also seems that all vibrational degrees of freedom of the molecule take part in this process. It is known that the appearance of differences in transition probabilities could be caused by additional attraction in interactions of molecules having dipole moments. Halogen derivatives have higher values of dipole moments than benzene. This difference could be responsible for the difference of transition probabilities and changes in the relaxation times. However, benzene derivatives with amino, nitro, and methyl groups and halides show the other type of relaxation.

  6. Relaxation in Physical Education Curricula.

    ERIC Educational Resources Information Center

    Coville, Claudia A.

    1979-01-01

    A theoretical framework for incorporating relaxation instruction in the physical education curriculum is presented based on the assumption that relaxation is a muscular-skeletal skill benefitting general motor skill acquisition. Theoretical principles, a definition of relaxation, and an analysis of stages of skill development are also used in the…

  7. Relaxation phenomena in disordered systems

    NASA Astrophysics Data System (ADS)

    Sciortino, F.; Tartaglia, P.

    1997-02-01

    In this article we discuss how the assumptions of self-similarity imposed on the distribution of independently relaxing modes, as well as on their amplitude and characteristic times, manifest in the global relaxation phenomena. We also review recent applications of such approach to the description of relaxation phenomena in microemulsions and molecular glasses.

  8. Rho-kinase inhibition improves vasodilator responsiveness during hyperinsulinemia in the metabolic syndrome.

    PubMed

    Schinzari, Francesca; Tesauro, Manfredi; Rovella, Valentina; Di Daniele, Nicola; Gentileschi, Paolo; Mores, Nadia; Campia, Umberto; Cardillo, Carmine

    2012-09-15

    In patients with the metabolic syndrome (MetS), the facilitatory effect of insulin on forearm vasodilator responsiveness to different stimuli is impaired. Whether the RhoA/Rho kinase (ROCK) pathway is involved in this abnormality is unknown. We tested the hypotheses that, in MetS patients, ROCK inhibition with fasudil restores insulin-stimulated vasodilator reactivity and that oxidative stress plays a role in this mechanism. Endothelium-dependent and -independent forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were assessed in MetS patients (n = 8) and healthy controls (n = 5) before and after the addition of fasudil (200 μg/min) to an intra-arterial infusion of insulin (0.1 mU/kg/min). In MetS patients (n = 5), fasudil was also infused without hyperinsulinemia. The possible involvement of oxidative stress in the effect of fasudil during hyperinsulinemia was investigated in MetS patients (n = 5) by infusing vitamin C (25 mg/min). In MetS patients, compared with saline, fasudil enhanced endothelium-dependent and -independent vasodilator responses during insulin infusion (P < 0.001 and P = 0.008, respectively), but not in the absence of hyperinsulinemia (P = 0.25 and P = 0.13, respectively). By contrast, fasudil did not affect vasoreactivity to ACh and SNP during hyperinsulinemia in controls (P = 0.11 and P = 0.56, respectively). In MetS patients, fasudil added to insulin and vitamin C did not further enhance vasodilation to ACh and SNP (P = 0.15 and P = 0.43, respectively). In the forearm circulation of patients with the MetS, ROCK inhibition by fasudil improves endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia; increased oxidative stress seems to be involved in the pathophysiology of this phenomenon. PMID:22829585

  9. Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta.

    PubMed

    Hansen, K; Nedergaard, O A

    1999-08-01

    The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nitro-L-arginine abolished the inhibitory effect of EDTA and ascorbic acid. Acetylcholine evoked a rapid concentration-dependent relaxation that recovered spontaneously and slowly, but fully, with time. Relaxation evoked by equieffective concentrations of carbachol and acetylcholine had the same time course. Cumulative addition of acetylcholine (10(-7)-3 x 10(-5) M) caused a marked relaxation that was reverted slightly at high concentrations. The relaxation was the same with rings derived from the upper, middle, and lower part of the thoracic aorta. Two consecutive concentration-response curves for acetylcholine obtained at a 2-h interval demonstrated a slight development of tachyphylaxis. The relaxation was inversely related to precontractile tension evoked by phenylephrine when expressed as a percentage, but independent when expressed as g tension. Storage of aorta in cold salt solution for 24 h did not alter the relaxation. EDTA and ascorbic acid did not alter the relaxation. It is concluded that (1) EDTA and ascorbic acid can not be used with impunity to stabilize catecholamines used as preconstriction agents; (2) the reversal of the acetylcholine-evoked relaxation is not due to hydrolysis of acetylcholine; (3) the relaxation is uniform in all segments of thoracic aorta; (4) cold storage of aorta does not alter the relaxation; and (5) acetylcholine releases the same amount of relaxing factor, irrespective of the precontractile tension. PMID:10691020

  10. The Effect of Timed Relaxation on Keyboarding Achievement. Research Bulletin No. 46-B.

    ERIC Educational Resources Information Center

    Matthews, Doris B.

    Research has shown that relaxation exercises produce physical changes in students. After relaxation exercises, students appear calmer, have reduced levels of anxiety, and are more responsive to instruction. In order to determine if relaxation exercises would improve the rate at which students learn keyboarding, a study was conducted in a South…

  11. Relaxing music for anxiety control.

    PubMed

    Elliott, Dave; Polman, Remco; McGregor, Richard

    2011-01-01

    The purpose of this investigation was to determine the characteristics of relaxing music for anxiety control. Undergraduate students (N=84) were instructed to imagine themselves in an anxiety producing situation while listening to a selection of 30 music compositions. For each composition, level of relaxation, the factors that either enhanced or detracted from its relaxing potential and the emotional labels attached were assessed. Participants were also asked to state which music components (e.g., tempo, melody) were most conducive to relaxation. Additional information was obtained through the use of a focus group of 6 undergraduate music students. This paper presents details on the characteristics of relaxing-music for anxiety control and emotional labels attached to the relaxing compositions. Furthermore, an importance value has been attached to each of the music components under scrutiny, thus providing an indication of which music components should receive greatest attention when selecting music for anxiety control. PMID:22097099

  12. Vascular relaxation induced by Eucommiae Ulmoides Oliv. and its compounds Oroxylin A and wogonin: implications on their cytoprotection action

    PubMed Central

    Akinyi, Mary; Gao, Xiu Mei; Li, Yu Hong; Wang, Bing Yao; Liu, Er Wei; Chai, Li Juan; JawoBah, Abdulai; Fan, Guan Wei

    2014-01-01

    The vascular relaxation action of Eucommiae Ulmoides Oliv. also known as Duzhong has been seen on arteries of the heart such as the aorta and the coronary artery which are elastic in nature. Duzhong is historically an active ingredient commonly used in hypertensive herbal prescriptions in China. This work investigated the vasodilating effect of Duzhong and its compounds (wogonin 10 μM and oroxylin-A) in the isolated intact rat heart, perfused retrograde according the method of Langendorff and the cytoprotective effect in EA.hy926 cell lines Coronary perfusion pressure was monitored with a pressure transducer connected to a side-arm of the aortic perfusion cannula. Duzhong induced vasorelaxation in a dose dependent manner, on precontracting the vessels with endothelin-1, Duzhong 10 mg/ml, wogonin 10 μM and oroxylin-A 10 μM could significantly lower the perfusion pressure in reference to positive control SNP, Duzhong induced vasodilation was not inhibited by L-NAME (nitric oxide inhibitor), but was significantly inhibited by Tetraethyl ammonium (TEA, a K+ channel blocker and almost abolished by potassium chloride. The underlying mechanism was carried out in EA.hy926 cell lines. When these cells were treated with H2O2, there was higher expression of NOX-4, TNF-α and COX-2 mRNA. However, wogonin treatment attenuated the mRNA of NOX-4, TNF-α and COX-2. Wogonin also upregulated the mRNA expression of CAT, SOD-1 and GSR in oxidative stress induced by H2O2 EA.hy926 cells. Duzhong and compounds can exert an in vitro relaxation effect of the coronary artery and improve the heart function in Langendorff apparatus. This action appears to be endothelium dependent but not NO mediated. Cell culture findings indicated that wogonin can exert vascular and cellular protection by scavenging Reactive Oxygen Species. PMID:25419347

  13. Renormalized reaction and relaxation rates

    NASA Astrophysics Data System (ADS)

    Gorbachev, Yuriy E.

    2016-06-01

    Impact of the non-equilibrium on the reaction and relaxation rates (called as generalized relaxation rates - GRR), for the spatially inhomogeneous gas mixture is considered. Discarding the assumption that the 'chemical' part of the collisional integral is a small correction to non-reactive part, the expression for the zero-order GRR is derived. They are represented as a renormalization of the traditional reaction and relaxation rates, which means mixing of all corresponding processes. Thus all reactions and relaxation processes are entangled.

  14. Comet Bursting Through Relaxation

    NASA Astrophysics Data System (ADS)

    Jacobson, Seth A.; Scheeres, D. J.

    2012-10-01

    Comets may be excited and occupy non-principal axis (complex) rotation states for a large fraction of their lifetimes. Many comet nuclei have been identified or are suspected to occupy non-principal axis (complex) rotation [Belton 2005, etc.] as well as have evolving rotation rates [Belton 2011, etc.]. Comet orbits drive these rotation states through cycles of excitation due to surface jets and relaxation due to time variable internal stresses that dissipate energy in the anelastic comet interior. Furthermore, relaxation from complex rotation can increase the loads along the symmetry axis of prolate comets. These loads stretch the body along the symmetry axis and may be the cause of the characteristic ``bowling pin’’ shape and eventually may lead to failure. This is an alternative model for comet bursting. Each cycle deposits only a small amount of energy and stress along the axis, but this process is repeated every orbit during which jets are activated. Our model for the evolution of comet nuclei includes torques due to a number of discrete jets located on the surface based on Neishtadt et al. [2002]. The model also includes internal dissipation using an approach developed by Sharma et al. [2005] and Vokrouhlicky et al. [2009]. These equations are averaged over the instantaneous spin state and the heliocentric orbit so the long-term evolution of the comet can be determined. We determine that even after the inclusion of internal dissipation there still exist non-principal axis equilibrium states for certain jet geometries. For ranges of dissipation factors and jet geometries, prolate comets are found to occupy states that have time variable internal loads over long time periods. These periodic loadings along the symmetry axis may lead to ``necking’’ as the body extends along the axis to release the stress and eventually disruption.

  15. TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXATION IN ACHALASIA: EVERYTHING BUT LES RELAXATION

    PubMed Central

    KWIATEK, Monika A.; POST, Jennifer; PANDOLFINO, John E.; KAHRILAS, Peter J.

    2009-01-01

    Background: In conducting clinical high resolution esophageal pressure topography (HREPT) studies we observed that after subjects sat upright between series of supine and upright test swallows, they frequently had a transient lower esophageal sphincter relaxation (tLESR). When achalasia patients were studied in the same protocol, they exhibited a similar HREPT event leading to the hypothesis that achalasics had incomplete tLESRs. Methods: We reviewed clinical HREPT studies of 94 consecutive non-achalasics and 25 achalasics. Studies were analyzed for a tLESR-like event during the study and, when observed, that tLESR-like event was characterized for the degree and duration of distal esophageal shortening, the degree of LES relaxation, associated crural diaphragm (CD) inhibition, esophageal pressurization, and upper esophageal sphincter (UES) relaxation. Results: 64/94 (68%) non-achalasics and 15/24 (63%) of achalasics had a pressure topography event after the posture change characterized by a prolonged period of distal esophageal shortening and/or LES relaxation. Events among the non-achalasics and achalasics were similar in terms of magnitude and duration of shortening and all were associated with CD inhibition. Similar proportions had associated non-deglutitive UES relaxations. The only consistent differences were the absence of associated LES relaxation and the absence of HREPT evidence of reflux among the achalasics leading us to conclude that their events were incomplete tLESRs. Conclusions: Achalasic patients exhibit a selective defect in the tLESR response suggesting preservation of all sensory, central, and efferent aspects of the requisite neural substrate with the notable exception of LES relaxation, a function of inhibitory (nitrergic) myenteric plexus neurons. PMID:19552630

  16. Measuring the Longitudinal NMR Relaxation Rates of Fast Relaxing Nuclei Using a Signal Eliminating Relaxation Filter

    NASA Astrophysics Data System (ADS)

    Hansen, D. Flemming; Led, Jens J.

    2001-08-01

    A new experiment for selective determination of the relaxation rates of fast relaxing NMR signals is presented. The experiment is derived from the conventional inversion recovery experiment by substituting the 180° inversion pulse of this experiment with a signal eliminating relaxation filter (SERF) consisting of three 180° pulses separated by two variable delays, Δ1 and Δ2. The SERF experiment allows a selective suppression of signals with relaxation rates below a given limit while monitoring the relaxation of faster relaxing signals. The experiment was tested on a sample of 20% oxidized plastocyanin from Anabaena variabilis, where the fast exchange of an electron between the reduced (diamagnetic) and the oxidized (paramagnetic) form results in a series of average signals with widely different relaxation rates. To ensure an optimum extraction of information from the experimental data, the relaxation rates were obtained from the SERF experiment by a simultaneous analysis of all the FIDs of the experiment using a fast linear prediction model method developed previously. The reliability of the relaxation rates obtained from the SERF experiment was confirmed by a comparison of the rates with the corresponding rates obtained from a conventional inversion recovery experiment.

  17. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.

    PubMed Central

    Minor, R L; Myers, P R; Guerra, R; Bates, J N; Harrison, D G

    1990-01-01

    We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF. Images PMID:2254462

  18. Postseismic relaxation and transient creep

    USGS Publications Warehouse

    Savage, J.C.; Svarc, J.L.; Yu, S.-B.

    2005-01-01

    Postseismic deformation has been observed in the epicentral area following the 1992 Landers (M = 7.3), 1999 Chi-Chi (M = 7.6), 1999 Hector Mine (M = 7.1), 2002 Denali (M = 7.9), 2003 San Simeon (M = 6.5), and 2004 Parkfield (M = 6.0) earthquakes. The observations consist of repeated GPS measurements of the position of one monument relative to another (separation ???100 km). The early observations (t < 0.1 year) are well fit by the function a' + c'log(t), where t is the time after the earthquake and a' and c' are constants chosen to fit the data. Because a log(t) time dependence is characteristic of transient (primary) creep, the early postseismic response may be governed by transient creep as Benioff proposed in 1951. That inference is provisional as the stress conditions prevailing in postseismic relaxation are not identical to the constant stress condition in creep experiments. The observed logarithmic time dependence includes no characteristic time that might aid in identifying the micromechanical cause.

  19. Stress Relaxation of Magnetorheological Fluids

    NASA Astrophysics Data System (ADS)

    Li, W. H.; Chen, G.; Yeo, S. H.; Du, H.

    In this paper, the experimental and modeling study and analysis of the stress relaxation characteristics of magnetorheological (MR) fluids under step shear are presented. The experiments are carried out using a rheometer with parallel-plate geometry. The applied strain varies from 0.01% to 100%, covering both the pre-yield and post-yield regimes. The effects of step strain, field strength, and temperature on the stress modulus are addressed. For small step strain ranges, the stress relaxation modulus G(t,γ) is independent of step strain, where MR fluids behave as linear viscoelastic solids. For large step strain ranges, the stress relaxation modulus decreases gradually with increasing step strain. Morever, the stress relaxation modulus G(t,γ) was found to obey time-strain factorability. That is, G(t,γ) can be represented as the product of a linear stress relaxation G(t) and a strain-dependent damping function h(γ). The linear stress relaxation modulus is represented as a three-parameter solid viscoelastic model, and the damping function h(γ) has a sigmoidal form with two parameters. The comparison between the experimental results and the model-predicted values indicates that this model can accurately describe the relaxation behavior of MR fluids under step strains.

  20. Biofeedback-Assisted Relaxation Training in the Elementary Classroom.

    ERIC Educational Resources Information Center

    Zaichkowsky, Linda B.; And Others

    1986-01-01

    Examined feasibility of training young elementary school children in stress responses and coping techniques. Findings indicated children can learn to control heart rate, respiration rate, and skin temperature responses by participating in a program that includes instruction on proper breathing; modified, progressive muscle relaxation; visual…

  1. Relaxation strategies for patients during dermatologic surgery.

    PubMed

    Shenefelt, Philip D

    2010-07-01

    Patient stress and anxiety are common preoperatively and during dermatologic procedures and surgeries. Stress and anxiety can occasionally interfere with performance of procedures or surgery and can induce hemodynamic instability, such as elevated blood pressure or syncope, as well as producing considerable discomfort for some patients. Detection of excess stress and anxiety in patients can allow the opportunity for corrective or palliative measures. Slower breathing, biofeedback, progressive muscular relaxation, guided imagery, hypnosis, meditation and music can help calm and rebalance the patient's autonomic nervous system and immune functioning. Handheld miniaturized heart rate variability biofeedback devices are now available. The relaxation response can easily be taught. Guided imagery can be recorded or live. Live rapid induction hypnosis followed by deepening and then self-guided imagery requires no experience on the part of the patient but does require training and experience on the part of a provider. Recorded hypnosis inductions may also be used. Meditation generally requires more prior experience and training, but is useful when the patient already is skilled in it. Live, guided meditation or meditation recordings may be used. Relaxing recorded music from speakers or headphones or live performance music may also be employed to ease discomfort and improve the patient's attitude for dermatologic procedures and surgeries. PMID:20677535

  2. Dynamics in supercooled polyalcohols: Primary and secondary relaxation

    NASA Astrophysics Data System (ADS)

    Döß, A.; Paluch, M.; Sillescu, H.; Hinze, G.

    2002-10-01

    We have studied details of the molecular dynamics in a series of pure polyalcohols by means of dielectric spectroscopy and 2H nuclear magnetic resonance (NMR). From glycerol to threitol, xylitol and sorbitol a systematic change in the dynamics of the primary and secondary relaxation is found. With increasing molecular weight and fragility an increase in the width of the α-peak is observed. Details of the molecular reorientation process responsible for the α-relaxation were exploited by two-dimensional NMR experiments. It is found that in the same sequence of polyalcohols the appearance of the secondary relaxation changes gradually from a wing type scenario to a pronounced β-peak. From NMR experiments using selectively deuterated samples the molecular origin of the secondary relaxation could be elucidated in more detail.

  3. Relaxation schemes for Chebyshev spectral multigrid methods

    NASA Technical Reports Server (NTRS)

    Kang, Yimin; Fulton, Scott R.

    1993-01-01

    Two relaxation schemes for Chebyshev spectral multigrid methods are presented for elliptic equations with Dirichlet boundary conditions. The first scheme is a pointwise-preconditioned Richardson relaxation scheme and the second is a line relaxation scheme. The line relaxation scheme provides an efficient and relatively simple approach for solving two-dimensional spectral equations. Numerical examples and comparisons with other methods are given.

  4. Effects of Cyclic Intermittent Hypoxia on ET-1 Responsiveness and Endothelial Dysfunction of Pulmonary Arteries in Rats

    PubMed Central

    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. PMID:23555567

  5. Dependence of Brownian and Néel relaxation times on magnetic field strength

    SciTech Connect

    Deissler, Robert J. Wu, Yong; Martens, Michael A.

    2014-01-15

    Purpose: In magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS) the relaxation time of the magnetization in response to externally applied magnetic fields is determined by the Brownian and Néel relaxation mechanisms. Here the authors investigate the dependence of the relaxation times on the magnetic field strength and the implications for MPI and MPS. Methods: The Fokker–Planck equation with Brownian relaxation and the Fokker–Planck equation with Néel relaxation are solved numerically for a time-varying externally applied magnetic field, including a step-function, a sinusoidally varying, and a linearly ramped magnetic field. For magnetic fields that are applied as a step function, an eigenvalue approach is used to directly calculate both the Brownian and Néel relaxation times for a range of magnetic field strengths. For Néel relaxation, the eigenvalue calculations are compared to Brown's high-barrier approximation formula. Results: The relaxation times due to the Brownian or Néel mechanisms depend on the magnitude of the applied magnetic field. In particular, the Néel relaxation time is sensitive to the magnetic field strength, and varies by many orders of magnitude for nanoparticle properties and magnetic field strengths relevant for MPI and MPS. Therefore, the well-known zero-field relaxation times underestimate the actual relaxation times and, in particular, can underestimate the Néel relaxation time by many orders of magnitude. When only Néel relaxation is present—if the particles are embedded in a solid for instance—the authors found that there can be a strong magnetization response to a sinusoidal driving field, even if the period is much less than the zero-field relaxation time. For a ferrofluid in which both Brownian and Néel relaxation are present, only one relaxation mechanism may dominate depending on the magnetic field strength, the driving frequency (or ramp time), and the phase of the magnetization relative to the

  6. Relaxation in glassforming liquids and amorphous solids

    SciTech Connect

    Angell, C. A.; Ngai, K. L.; McKenna, G. B.; McMillan, P. F.; Martin, S. W.

    2000-09-15

    The field of viscous liquid and glassy solid dynamics is reviewed by a process of posing the key questions that need to be answered, and then providing the best answers available to the authors and their advisors at this time. The subject is divided into four parts, three of them dealing with behavior in different domains of temperature with respect to the glass transition temperature, T{sub g}, and a fourth dealing with ''short time processes.'' The first part tackles the high temperature regime T>T{sub g}, in which the system is ergodic and the evolution of the viscous liquid toward the condition at T{sub g} is in focus. The second part deals with the regime T{approx}T{sub g}, where the system is nonergodic except for very long annealing times, hence has time-dependent properties (aging and annealing). The third part discusses behavior when the system is completely frozen with respect to the primary relaxation process but in which secondary processes, particularly those responsible for ''superionic'' conductivity, and dopart mobility in amorphous silicon, remain active. In the fourth part we focus on the behavior of the system at the crossover between the low frequency vibrational components of the molecular motion and its high frequency relaxational components, paying particular attention to very recent developments in the short time dielectric response and the high Q mechanical response. (c) 2000 American Institute of Physics.

  7. Phase transitions in semidefinite relaxations

    PubMed Central

    Javanmard, Adel; Montanari, Andrea; Ricci-Tersenghi, Federico

    2016-01-01

    Statistical inference problems arising within signal processing, data mining, and machine learning naturally give rise to hard combinatorial optimization problems. These problems become intractable when the dimensionality of the data is large, as is often the case for modern datasets. A popular idea is to construct convex relaxations of these combinatorial problems, which can be solved efficiently for large-scale datasets. Semidefinite programming (SDP) relaxations are among the most powerful methods in this family and are surprisingly well suited for a broad range of problems where data take the form of matrices or graphs. It has been observed several times that when the statistical noise is small enough, SDP relaxations correctly detect the underlying combinatorial structures. In this paper we develop asymptotic predictions for several detection thresholds, as well as for the estimation error above these thresholds. We study some classical SDP relaxations for statistical problems motivated by graph synchronization and community detection in networks. We map these optimization problems to statistical mechanics models with vector spins and use nonrigorous techniques from statistical mechanics to characterize the corresponding phase transitions. Our results clarify the effectiveness of SDP relaxations in solving high-dimensional statistical problems. PMID:27001856

  8. Phase transitions in semidefinite relaxations.

    PubMed

    Javanmard, Adel; Montanari, Andrea; Ricci-Tersenghi, Federico

    2016-04-19

    Statistical inference problems arising within signal processing, data mining, and machine learning naturally give rise to hard combinatorial optimization problems. These problems become intractable when the dimensionality of the data is large, as is often the case for modern datasets. A popular idea is to construct convex relaxations of these combinatorial problems, which can be solved efficiently for large-scale datasets. Semidefinite programming (SDP) relaxations are among the most powerful methods in this family and are surprisingly well suited for a broad range of problems where data take the form of matrices or graphs. It has been observed several times that when the statistical noise is small enough, SDP relaxations correctly detect the underlying combinatorial structures. In this paper we develop asymptotic predictions for several detection thresholds, as well as for the estimation error above these thresholds. We study some classical SDP relaxations for statistical problems motivated by graph synchronization and community detection in networks. We map these optimization problems to statistical mechanics models with vector spins and use nonrigorous techniques from statistical mechanics to characterize the corresponding phase transitions. Our results clarify the effectiveness of SDP relaxations in solving high-dimensional statistical problems. PMID:27001856

  9. Inhibition of the release of endothelium-derived relaxing factor in vitro and in vivo by dipeptides containing NG-nitro-L-arginine.

    PubMed Central

    Thiemermann, C.; Mustafa, M.; Mester, P. A.; Mitchell, J. A.; Hecker, M.; Vane, J. R.

    1991-01-01

    1. We have shown that dipeptides containing NG-nitro-L-arginine (NO2Arg) inhibit the biosynthesis of endothelium-derived relaxing factor (EDRF) in vitro and in vivo. 2. In anaesthetized rats, intravenous administration at 1-30 mg kg-1 of the methyl ester of NO2Arg, NO2-Arg-L-phenylalanine (NO2Arg-Phe), L-alanyl-NO2Arg (Ala-NO2Arg) or NO2Arg-L-arginine (NO2Arg-Arg) produced dose-related increases in mean arterial blood pressure (MABP) which were unaffected by D-arginine (D-Arg; 20 mg kg-1 min-1 for 15 min), but prevented by co-infusions of L-arginine (L-Arg; 20 mg kg-1 min-1 for 15 min) or by their parent dipeptides. 3. NO2Arg methyl ester, NO2Arg-Phe methyl ester or Ala-NO2Arg methyl ester (10 mg kg-1, i.v.) also inhibited the reduction in MABP caused by the endothelium-dependent vasodilator, acetylcholine (30 micrograms kg-1 min-1 for 3 min), but not those induced by glycerly trinitrate (20 micrograms kg-1 min-1 for 3 min) or iloprost (6 micrograms kg-1 min-1 for 3 min) which act directly on the vascular smooth muscle. 4. Moreover, NO2Arg methyl ester, NO2Arg-Phe methyl ester or NO2Arg-Arg methyl ester (100 microM) inhibited the acetylcholine-induced relaxation of rabbit aortic strips, and NO2Arg-Phe methyl ester (30 microM) blocked the stimulated (bradykinin, 30 pmol) release of EDRF from bovine aortic endothelial cells grown on microcarrier beads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1786515

  10. Multigrid Methods for Mesh Relaxation

    SciTech Connect

    O'Brien, M J

    2006-06-12

    When generating a mesh for the initial conditions for a computer simulation, you want the mesh to be as smooth as possible. A common practice is to use equipotential mesh relaxation to smooth out a distorted computational mesh. Typically a Laplace-like equation is set up for the mesh coordinates and then one or more Jacobi iterations are performed to relax the mesh. As the zone count gets really large, the Jacobi iteration becomes less and less effective and we are stuck with our original unrelaxed mesh. This type of iteration can only damp high frequency errors and the smooth errors remain. When the zone count is large, almost everything looks smooth so relaxation cannot solve the problem. In this paper we examine a multigrid technique which effectively smooths out the mesh, independent of the number of zones.