Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane potential of porcine coronary artery with an without endothelium, conducting experiments with addition of indomethacin (10(-5) M) to rule out involvement of prostanoids. Average resting membrane potential (RMP) in porcine coronary artery was -51.1 +/- 0.2 and -50.3 +/- 0.2 mV, with and without endothelium, respectively. AD agonists at 10(-5) M caused a significant increase in RMP to -69.5 +/- 0.2 mV for AD, to -82.2 +/- 0.3 mV for CAD, and to -81.2 +/- 0.3 mV for NECA in porcine coronary arteries with intact endothelium. Moreover, AD agonists at 10(-5) M caused a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for AD, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without endothelium. The average RMP for human coronary artery with and without endothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitatively, similar effects of AD and its analogues were observed in two human coronary arteries. The AD receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 10(-5) M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coronary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synthase inhibitors N-monomethyl-L-arginine (L-NMMA, 10(-5) M) and N-nitro-L-arginine methylester (L-NAME, 10(-5) M), and the effect of L-NAME was reversed by L-arginine (L-ARG, 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1995 Feb
PMID:Role of endothelium in hyperpolarization of coronary smooth muscle by adenosine and its analogues. 775 49

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.
J Cardiovasc Pharmacol 1994 Dec
PMID:Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats. 789 82

The effects of chronic therapy with the angiotensin-converting enzyme (ACE) inhibitor trandolapril and/or Ca2+ antagonist verapamil on endothelial and vascular smooth muscle (VSM) function were studied in spontaneously hypertensive, stroke-prone rats (SHRSP). Dosages decreasing systolic blood pressure (SBP) by 20% were administered orally (p.o.) by gavage as monotherapy or combination therapy for 8 weeks, beginning at age 6 weeks. Combination therapy dosages were the same as those used in monotherapy (trandolapril 0.7 mg/kg/day verapamil 20 mg/kg/day) in one group; the second group received only half the monotherapy dosage. The study was placebo-controlled and performed in parallel groups. Isometric tension was measured in aortic rings suspended in organ chambers (95% C2/5% CO2; 37 degrees C). SBP decreased in all groups, as compared with placebo [30-47 mm Hg, analysis of variance (ANOVA), p < 0.05], but decrease was more pronounced in rats receiving high-dose combination (76 mm Hg, ANOVA, p < 0.05). In norepinephrine (NE)-contracted rings, endothelium-dependent relaxation to acetylcholine (ACh) was augmented similarly with all forms of therapy (maximal relaxations 89-94%) as compared with placebo (64 +/- 6%, p < 0.05). In contrast, the response to sodium nitroprusside (SNP) was similar in all groups (NS). In quiescent rings, ACh elicited endothelium-dependent contractions (in the presence of N omega-monomethyl-L-arginine, L-NAME) that were not affected by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 Dec
PMID:Endothelial dysfunction in aorta of the spontaneously hypertensive, stroke-prone rat: effects of therapy with verapamil and trandolapril alone and in combination. 789 83

Endothelium-derived nitric oxide (EDNO) has been implicated in the modulation of coronary arterial tone. The aim of this study was to determine if metabolic coronary vasodilation induced by pacing tachycardia is altered by the inhibition of EDNO synthesis. Before and after the intracoronary infusion of an inhibitor of EDNO synthesis (N omega-nitro-L-arginine-methyl-ester, L-NAME), changes in coronary blood flow (CBF), regional myocardial blood flow (MBF), and myocardial oxygen consumption (MVO2) were measured in anesthetized dogs in response to atrial pacing tachycardia. Increasing the heart rate from 109 +/- 10 to 160 beats/min by pacing produced significant increases in CBF (p < 0.05), MVO2 (p < 0.05), and MBF in each sublayer of the myocardium (p < 0.05). L-NAME did not alter the pacing-induced increases in CBF, MVO2, or regional MBF. In addition, the ratio of the tachycardia-induced increase in CBF to the increase in MVO2 was not changed by L-NAME. The coronary vasodilation evoked by acetylcholine was attenuated by L-NAME (p < 0.05). However, the response to sodium nitroprusside was not altered. These results suggest that EDNO does not play a primary role in the mechanism mediating metabolic coronary vasodilation induced by pacing tachycardia in dogs.
J Cardiovasc Pharmacol 1995 Sep
PMID:Endothelium-derived nitric oxide does not modulate metabolic coronary vasodilation induced by tachycardia in dogs. 858 86

The vascular effects of endothelin-1 (ET-1; ETA/ETB agonist), sarafotoxin 6b (S6b; ETA agonist), and IRL 1620 (ETB agonist) were investigated in the isolated canine liver arterial circuit before and after infusions of indomethacin (cyclo-oxygenase inhibitor) and N omega L-nitro arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor). Norepinephrine (NE) was used as vasconstrictor control agent. The portal vein, hepatic artery, and vena cava were cannulated in vitro and the liver was perfused via the hepatic artery and portal vein with oxygenated (95%) O2/5% CO2) Krebs solution at 37 degrees C. Intra-arterial bolus injections of either ET-1 (0.4-400 pmol) or S6b (0.4-400 pmol) induced dose-dependent and long-lasting vasoconstriction accompanied by significant prostacyclin release. The vasoconstrictor responses to these peptides were slightly increased during infusion of indomethacin. Subsequent infusion of L-NAME potentiated both ET-1- and S6b-induced vasoconstriction (p < 0.05). IRL 1620 (up to 1.2 nmol) had no effect on the hepatic arterial vascular resistance even during indomethacin and L-NAME infusions. Infusion of the ETA receptor antagonist FR-139317 (0.3 microM) markedly reduced both ET-1- and S6b-induced vasoconstriction without affecting that evoked by NE. Our results indicate that pressor responses to ET-1 and S6b in the isolated canine liver are modulated by concomitant release of vasodilator mediators, including prostacyclin and nitric oxide. These effects appear to depend primarily on the activation of ETA receptor subtypes. IRL 1620 (but not ET-1) induced a significant release of hemoglobin into the venous effluent, suggesting that ETB receptors are located in the venous side of the intrahepatic circulation.
J Cardiovasc Pharmacol 1995
PMID:Role of endothelin ETA and ETB receptors in the arterial vasculature of the isolated canine liver. 858 63

This study evaluated the effects of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively) and the interactions with other local vasoactive systems in the regulation of renal regional blood flow. CBF and MBF were measured simulataneously by laser-Doppler flowmetry in anesthetized Wistar rats. Administration of ET-1 (1.0 nmol/kg, i.v.) produced a decrease in CBF (delta = -20%) and at the same time increased MBF (delta = +24%). In the presence of nitric oxide (NO) blockade by L-NAME, the vasodilatory effect of ET-1 on MBF was completely blocked and actually reversed (delta = -19%), whereas the cortical vasconstrictor effect was potentiated (delta = -31%). Cycloxygenase inhibition with indomethacin attenuated the vasodilator effect of ET-1 on MBF (delta = +12%) but did not affect the changes in CBF. Therefore, ET-1 exerts a differential effect on intrarenal regional blood flow, i.e., a decrease in CBF and an increase in MBF. The medullary vasodilator action of the peptide is dependent on an intact NO system and, to a lesser extent, on prostaglandin synthesis.
J Cardiovasc Pharmacol 1995
PMID:Differential effect of endothelin-1 on renal regional blood flow: role of nitric oxide. 858 64

In the present study we characterized the effects of and receptors for endothelins (ETs) in the guinea pig mesenteric arterial and venous vasculatures. Endothelin-1 (ET-1) (10-500 pmol) induced a dose-dependent increase of perfusion pressure of the arterial and venous beds. ET-2 (10-500 pmol) also induced a dose-dependent vasoconstriction on both sides of the mesenteric circulation but was less potent than ET-1. In contrast, ET-3 (10-1,000 pmol) and the selective ETB agonist IRL 1620 (1,000 pmol) were inactive. A nitric oxide (NO) synthase inhibitor, L-NAME (200 microM), markedly potentiated the vasoconstrictor response to ET-1 (100 pmol arterial side; 1,000 pmol venous side) on both sides of the mesenteric vasculature. In precontracted mesenteric vessels, ET-1 (0.1-5 pmol) and IRL-1620 (1,000 pmol) induced a small yet significant vasodilation only on the arterial side. Furthermore, BQ-123 (1 microM), an ETA receptor antagonist, significantly reduced the ET-1-induced venoconstriction and completely blocked the vasoconstriction on the arterial side. Hence, the arterial and venous mesenteric vessels of the guinea pig respond to ETs by activation of ETA receptors. Furthermore, the endothelium may act as a physiologic barrier to the constrictor effects of ETs by basally releasing NO.
J Cardiovasc Pharmacol 1995
PMID:Characterization of receptors for endothelins in the guinea pig mesenteric vasculature. 858

Chronic nitric oxide (NO) blockade promotes progressive hypertension, marked renal vasoconstriction, and glomerular and renal interstitial injury. Inhibition of the renin/angiotensin system prevents only partially the functional and structural abnormalities associated with this model. Because endothelin (ET) is a powerful endogenous vasoconstrictor and promitogen, we examined the hypothesis that it might also mediate the hemodynamic and renal structural effects of chronic NO blockade. Four groups of 16 adult male Munich-Wistar rats were studied. Group C received daily i.p. saline injections and no drug treatment. Group C+FR received daily i.p. injections of the ETA inhibitor FR139317, 32 mg/kg. Group NAME received the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 65 mg/kg/day in the drinking water, and group NAME+FR received both L-NAME and FR139317. At 2 weeks of treatment, renal and systemic hemodynamic parameters assessed under anesthesia were similar in Groups C and C+FR. Rats of Group NAME exhibited systemic hypertension and renal vasoconstriction characteristic of this model. FR139317 was ineffective in preventing these abnormalities in Group NAME+FR. In eight additional rats of each group observed at 30 days, FR139317 treatment was equally inactive in the prevention of glomerular collapse and interstitial expansion, the two chief modalities of renal injury in this model. These results suggest that ET does not participate, at least via the ETA receptor, in the pathogenesis of hypertension, renal dysfunction, or renal injury associated with the chronic NO inhibition model.
J Cardiovasc Pharmacol 1995
PMID:Do ETA receptors participate in the hemodynamic and renal effects of chronic nitric oxide blockade? 858 46

The therapeutical use of cyclosporine A (CsA) is hampered by the development of nephrotoxicity characterized by a marked increase in renal vascular resistance (RVR). We investigated vascular functions in kidneys of rats treated with CsA. The ex vivo vascular reactivity of kidneys from control rats and animals treated subacutely with CsA [50 mg/kg/day subcutaneously (s.c.) for 16-21 days] or an olive oil vehicle (1 ml/kg) was analyzed in male Wistar rats. The right kidney was isolated and perfused with Tyrode's or Krebs solution in an open circuit. The effects of acetylcholine (Ach), fenoldopam (FEN), and sodium nitroprusside (SNP) on norepinephrine (NE) preconstricted kidneys were studied. In control kidneys (untreated or vehicle-treated), Ach induced a relaxation (EC50 = 0.56 +/- 0.05 x 10(-9)M; Emax = 88.2 +/- 2.1% decrease in the vascular tone restored by NE) which was endothelium-dependent [near-complete abolition after treatment with a detergent, 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS) treatment] but only partially inhibited by indomethacin (EC50 = 1.71 +/- 0.39 x 10(-9)M, p < 0.05; Emax = 87.1 +/- 4.9%, NS) or indomethacin with NG-nitro-L-arginine methyl ester (L-NAME: EC50 = 1.04 +/- 0.38 x 10(-9)M, NS; Emax = 63.8 +/- 2.5%, p < 0.01). CsA treatment induced a marked decrease in creatinine clearance and natriuresis measured in vivo but had no effect on systolic blood pressure (SBP). In CsA-treated rats, Ach-induced renal relaxation was partially blunted (EC50 = 1.88 +/- 0.34 x 10(-9)M, p < 0.01; Emax = 82.8 +/- 4.6, NS), with both a defect in prostaglandin (PG) and nitric oxide (NO)-related responses. CsA treatment had no effect on endothelium-independent relaxations induced by FEN and SNP. These results show that subacute CsA treatment selectively impairs renal endothelium-dependent relaxation related to PGs and NO release.
J Cardiovasc Pharmacol 1995 Dec
PMID:Endothelium-dependent relaxation in the isolated rat kidney: impairment by cyclosporine A. 860 21

Vasoconstrictor responses to endothelin-1 (ET-1) and the ETB receptor agonist sarafotoxin S6c (SXS6c) were investigated in the main pulmonary artery and pulmonary artery branch removed from rats previously exposed to 10% O2 [chronic hypoxic (CH) rats] or room air (control rats) for 2 weeks. The effects of nitric oxide synthase (NOS) inhibition with L-Nomega-nitroarginine methyl ester (L-NAME) (100 microM) on ET receptor-induced responses in these arteries were also investigated. In control rats, in rings of main pulmonary arteries and pulmonary artery branches. ET-1 induced vasoconstrictor responses. These responses were mediated by the ETA receptor as they were antagonized by the ETA receptor antagonist FR 139317 whereas SXS6c did not vasoconstrict. Chronic hypoxia had no effect on the sensitivity of the main pulmonary arteries to ET-1, whereas small vasoconstrictor responses to SCS6c were evident. ET-1 was more potent in the CH rat pulmonary artery branches than in controls. SXS6c also caused vasoconstriction with a maximum response 30% of that to ET-1 in both endothelium-intact and endothelium-denuded vessels. L-NAME increased the sensitivity to ET-1 in the CH rat main pulmonary arteries and increased the responses to low concentrations of ET-1 in the control rat main pulmonary arteries but did not affect any ET-1 responses in any other vessels. It did disclose responses to SXS6c in control rat main pulmonary arteries. L-NAME itself increased vascular tone to a greater extent in CH rat pulmonary arteries than in controls. In preconstricted pulmonary arteries, however, relaxations to acetylcholine (ACh) were diminished in the CH rats as compared with their controls. All pulmonary artery branches, denuded of their vascular endothelium, relaxed to sodium nitroprusside (SNP) and therefore exhibited endogenous vascular tone. This effect was greatest in the pulmonary artery branches from the CH rats. The results suggest that rat large pulmonary artery responses to ET-1 are normally mediated by ETA receptors. Pulmonary hypertension can potentiate ETA receptor-mediated vasoconstriction and facilitate ETB receptor-mediated vasoconstriction. Endogenous NO may normally suppress ETA receptor-mediated responses in rat main pulmonary arteries. Rat pulmonary arteries exhibit endogenous tone, which is increased by exposure to chronic hypoxia.
J Cardiovasc Pharmacol 1995 Nov
PMID:Effects of pulmonary hypertension on vasoconstrictor responses to endothelin-1 and sarafotoxin S6C and on inherent tone in rat pulmonary arteries. 863 98


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