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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurohumoral changes influencing peripheral vascular resistance play a major role in congestive heart failure (CHF). We studied vascular function in 1-year-old cardiomyopathic syrian hamsters with pulmonary congestion and age-matched control hamsters. Aorta and mesenteric resistance arteries were suspended in organ chambers and myographs, respectively, for isometric tension recording. In aorta and mesenteric resistance arteries, contractile responses to norepinephrine (NE) were comparable in cardiomyopathic hamsters and controls. After inhibition of nitric oxide (NO) formation with nitro-L-arginine methylester (L-NAME), contractions to NE were enhanced in aorta of cardiomyopathic hamsters (p < 0.05); no effect was noted in controls or mesenteric resistance arteries. Low doses of endothelin-1 (ET-1 10(-10)-10(-9) M) caused stronger contractions in aorta of cardiomyopathic hamsters as compared with controls (p < 0.05). The sensitivity and maximal contraction to ET were more pronounced in mesenteric resistance arteries as compared with aorta in both cardiomyopathic and control hamsters (p < 0.05-0.001). In both aorta and mesenteric resistance arteries, acetylcholine (ACh 10(-9)-10(-5) M) induced concentration-dependent relaxation, which was prevented by L-NAME (p < 0.001). Maximal endothelium-dependent relaxation was more pronounced in aorta of cardiomyopathic hamsters (p < 0.05), but not different in mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 Jun
PMID:Activity of the L-arginine/nitric oxide pathway and endothelin-1 in experimental heart failure. 752 83

We investigated the effect of hypoxia on acetylcholine (ACh) stimulated, endothelium-derived relaxing factor/nitric oxide (EDRF/NO)-dependent relaxation, and on basal tension in rat aortic rings. ACh (10(-9)-10(-6) M)-mediated relaxation at high [95%, Emax -76.2 +/- 4.5% of phenylephrine (PE)-induced constriction] and normal (20%, Emax -81.2 +/- 3.6%) O2 levels was inhibited by hypoxia (5%, Emax -36.2 +/- 7.2%); residual hypoxic relaxation was blocked by the K+ channel antagonist glibenclamide. To address whether O2 influenced EDRF/NO and K+ channel contributions to basal tone, the effect of stepwise reduction of available O2 (95, 20, 5, and 0%) was studied in intact and endothelial cell (EC)-denuded rings. The effects in these rings were compared with results of the same progressive reduction in O2 in the presence of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) or glibenclamide (10(-4) M). EC-intact and EC-denuded rings constricted to 0.80 +/- 0.10 and 1.41 +/- 0.15 g, respectively. Reducing O2 to 20% had no significant effect on vascular tension, but 5% caused constriction (p < 0.05) in EC-intact rings (0.90 +/- 0.15 g). This hypoxic vasoconstriction was blocked by L-NAME, but not by glibenclamide, suggesting that hypoxic vasoconstriction was mediated by withdrawal of EDRF/NO. In contrast, EC-denuded rings showed a significant relaxant response at 5% O2. When O2 was then reduced further (95% N2/5% CO2), both EC-intact and EC-denuded rings relaxed, and this relaxation reached baseline tension (0.10 +/- 0.1 g).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 Oct
PMID:Influence of oxygen on endothelium-derived relaxing factor/nitric oxide and K(+)-dependent regulation of vascular tone. 752 42

We wished to test the hypothesis of a connection existing between inducible nitric oxide (NO) synthesis and production of extracellular matrix proteins in endothelial cells (EC). We recently reported that the inducible-NO pathway contributes to cytokine-induced enhancement of tumor cell (TC) adhesion to cultured vascular endothelium, independent of changes in E-selectin expression on endothelial cells (EC). We now show that inducible NO-synthase is involved in enhancing fibronectin production by EC. Indeed, fibronectin synthesis and secretion increased both in the EA.hy926 EC line and in human umbilical vein EC (HUVEC) after prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma). This effect was reversed by the reported inhibitor of NO synthase N omega-nitro-L-arginine methyl ester (L-NAME 10(-5) M). The two cytokines exerted no additive effect, suggesting that they trigger a common metabolic pathway. NO production by cytokine-stimulated EC was dependent on the inducible NO-pathway, as demonstrated by studies of EC-dependent inhibition of platelet aggregation. This inhibition was also evident in calcium-free medium and was reversed by L-NAME and by two inhibitors of protein synthesis that are reported to block the inducible-NO synthase, such as dexamethasone (Dex 10(-7) M) and cycloheximide (Chx 10(-6) M). We conclude that modulation of the inducible NO-synthase may regulate matrix protein production by vascular endothelium during inflammation.
J Cardiovasc Pharmacol 1994 Dec
PMID:Inducible nitric oxide synthase modulates fibronectin production in the EA.hy926 cell line and cultured human umbilical vein endothelial cells. 753 52

In a previous study, we demonstrated that adenosine plays an important role in the central control of the cardiovascular system with involvement of adenosine A2 rather than A1 subtype receptors. In the present study, we investigated the putative relationship between nitric oxide (NO) and adenosine in the central and peripheral control of the cardiovascular system. Adult male normotensive anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1-purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2-purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1-0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.). CPCA and CHA induced a significant and dose-dependent decrease in arterial blood pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L-arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v. and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the central nervous system (CNS) and at the peripheral level by pretreatment with L-arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover, intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1995 Jun
PMID:Nitric oxide participates in the hypotensive effect induced by adenosine A2 subtype receptor stimulation. 756 26

Elevations in plasma angiotensin II (AngII) are associated with an efflux of plasma macromolecules into the perivascular and contiguous interstitial space. Whether this exudative response is related to associated hypertension or another effect of AngII is uncertain. We therefore monitored plasma and cardiac lymph total protein, albumin and fibronectin and calculated transvascular clearances for total protein (TVPC) and albumin (TVAC) and lymph fibronectin transport (LFT) every 30 min in open-chested, instrumented dogs. After baseline observations were obtained over 30 min, pressor (250 ng.kg.min-1) or nonpressor (11 ng.kg.min-1) doses of AngII were given intravenously for 90 min. Saline-treated, instrumented dogs served as controls. To address a potential secondary effect of AngII on vascular protein clearance, we monitored lymph prostaglandin E2 and cGMP (a marker of released nitric oxide, NO). At > or = 30 min, each dose of AngII was associated with a significant (P < or = 0.05) and comparable increase in TVPC, TVAC and LFT over baseline, indicating that increase in protein clearance was not related to elevated arterial pressure. Lymph cGMP rose significantly (P < or = 0.05) at 30 min for each dose of AngII and remained elevated thereafter. Lymph PGE2 was increased at > or = 60 min (P < or = 0.05) but only with the pressor dose. To determine the contribution of NO and PGE2 on AngII-induced transcoronary protein clearance, each dose of AngII was accompanied by co-administration of either the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or the cyclo-oxygenase inhibitor, indomethacin. L-NAME completely inhibited the release of cGMP and the increase in protein clearance was not seen. Indomethacin suppressed the release of PGE2, but did not prevent the increase in protein clearance. Thus, AngII-induced increase in transcoronary protein clearance is not related to arterial hypertension or the release of PGE2, but instead appears to be mediated by NO release.
Cardiovasc Res 1995 Aug
PMID:Angiotensin-II-induced increase in transcoronary protein clearance: role of hypertension vs. nitric oxide or cyclo-oxygenase products. 758 17

Ischemic preconditioning (PC) has been shown to limit ischemia- and reperfusion-induced arrhythmias. We wished to determine whether the antiarrhythmic effect of PC would be affected by inhibition of the L-arginine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reperfusion were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of PC (three cycles of 2-min coronary artery occlusion and 5-min reperfusion) on development of reperfusion-induced arrhythmias after 5-min coronary artery occlusion was studied in 12 rats. In 24 other rats, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i.v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 100 mg/kg i.v., n = 12) was administered to rats 5 min before coronary artery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent group to 17%, decreased the incidence of ventricular tachycardia (VT) from 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solvent group, respectively). L-NAME and L-NMMA did not significantly affect the protective effect of PC on reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1995 Apr
PMID:Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway? 759 18

We investigated vasodilator responses to acetylcholine (ACh) in isolated mesenteric vascular bed preparations (preconstricted with methoxamine) of young (2 months) and old (18 months) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). ACh produced a similar dose-dependent vasorelaxant effect in preparations from both 2-month old normotensive and hypertensive rats. This vasodilator response to ACh decreased with age, especially in hypertensive animals. In preparations from young WKY, the vasorelaxant effect of ACh was not affected by 100 microM NG-nitro-L-arginine methyl ester (L-NAME), and was only slightly reduced by 500 microM L-NAME. The K+ channel blocker tetraethylammonium (TEA 2.5-10 mM) concentration-dependently antagonized the ACh-induced vasodilation in the same preparations. In preparations obtained from aged WKY animals, as well as in those from young and aged SHR animals, ACh-induced vasodilation was significantly and concentration-dependently reduced by 100 and 500 microM L-NAME. On the other hand, TEA induced a lesser antagonistic effect than that observed in young normotensive animals. In preparations preconstricted with 80 mM KCl, ACh caused vasodilation that was weaker in preparations from young WKY than in those from aged WKY; on the contrary, ACh was more effective in young than in aged SHR. These results confirm that the vasodilating response to ACh decreases with age and hypertension and suggest that the main mechanism responsible for the effect of ACh in vessels of young normotensive animals consists of activation of K+ channels. In preparations from old normotensive, as well as in those from young and old hypertensive animals, ACh induces vasorelaxation mainly through nitric oxide (NO) release.
J Cardiovasc Pharmacol 1995 Apr
PMID:Roles of nitric oxide and endothelium-derived hyperpolarizing factor in vasorelaxant effect of acetylcholine as influenced by aging and hypertension. 759 28

This study examines the hypothesis that oxygen radicals down-regulate splanchnic nitric oxide synthesis and contribute to splanchnic vasoconstriction following hemorrhage/reperfusion injury. Anesthetized rats underwent placement of flow probes around the superior mesenteric artery and abdominal aorta. Animals were bled to 30 mmHg for 30 min, reperfused without or with superoxide dismutase, an oxygen radical scavenger, 15 min before reperfusion and compared with sham-treated rats. Animals were sequentially treated with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at 10 mg/kg and L-arginine, a nitric oxide precursor, at 200 mg/kg or 400 mg/kg. L-NAME increased systemic pressure and decreased superior mesenteric artery blood flow whereas L-arginine decreased arterial pressure and increased superior mesenteric artery blood flow in the sham animals. Hemorrhage/reperfusion injury attenuated the pressure and superior mesenteric artery blood flow changes following L-NAME and L-arginine dosing, which was reversed by superoxide dismutase treatment. These data suggest that oxygen free radicals regulate splanchnic nitric oxide synthesis, thus contributing to splanchnic vasoconstriction following hemorrhage/reperfusion injury.
Cardiovasc Surg 1995 Apr
PMID:Oxygen free radicals regulate splanchnic nitric oxide synthesis and blood flow. 760 8

We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and histamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 microM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 microM apamin but not by 250 nM dendrotoxin or 10 microM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K+ PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluorohexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1993 Mar
PMID:Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. 768 3

The effect of chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME) on cutaneous ear blood flow (EBF) in the rabbit was examined in vivo with use of laser Doppler flowmetry. Additionally, the efficacy of inhibition of NO by L-NAME was studied ex vivo in isolated preparations of aortic rings from these rabbits. Before surgical implantation of osmotic pumps loaded with L-NAME, resting EBF was not significantly different in rabbits selected for control or L-NAME treatment. Although chronic L-NAME treatment had no significant effect on resting core temperature, resting EBF was reduced significantly in L-NAME-treated rabbits as compared with EBF in control rabbits. Short-term body warming for 10-20 min caused a significant increase in EBF, but not in body temperature, to levels that were not significantly different between groups at 0, 1 and 2 weeks. Prolonged body warming for a further 30-40 min produced a rise in body temperature and a further increase in EBF of 22% to levels that were not significantly different in control and L-NAME-treated groups. Acetylcholine-induced relaxations of aortic rings and levels of cyclic GMP were significantly reduced in L-NAME-treated rabbits as compared with control rabbits, whereas relaxations to sodium nitroprusside were enhanced significantly. These findings demonstrate that the synthesis of NO can be inhibited chronically in the rabbit and are consistent with the concept that NO participates in the control of skin blood flow by counteracting vasoconstrictor tone but not in the vasodilation induced by body warming.
J Cardiovasc Pharmacol 1993 Aug
PMID:Chronic inhibition of nitric oxide production augments skin vasoconstriction in the rabbit ear. 769 70


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