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

1. The role of nitric oxide in the coronary circulation under basal conditions and when exposed to various vasodilator stimuli was studied in instrumented, anaesthetized goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 12 goats, left circumflex coronary blood flow (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (3-4, or 8-10 mg kg-1 injected i.v.) decreased resting coronary blood flow by 20 and 28%, increased mean arterial pressure by 23 and 30% and increased coronary vascular resistance by 47 and 65%, respectively, without affecting heart rate, or blood gases or pH. These haemodynamic effects were reversed by L-arginine (200-300 mg kg-1 by i.v. injection, 5 goats). 3. Acetylcholine (0.001-0.1 micrograms), sodium nitroprusside (0.01-0.3 mg), and diazoxide (0.1-3 mg), injected intracoronarily in 6 goats, produced dose-dependent increases in coronary blood flow; sodium nitroprusside (0.1-0.3 mg) also caused hypotension and tachycardia. 4. During the effects of L-NAME, the coronary vasodilatation to acetylcholine was attenuated, to sodium nitroprusside was increased, and to diazoxide was unaffected, in comparison with control conditions. The hypotensive effects of sodium nitroprusside were also increased during treatment with L-NAME. 5. Graded coronary hyperaemic responses occurred after 5, 10 or 20 s of coronary occlusion. The magnitude of hyerpaemia for each occlusion duration was increased during treatment with L-NAME, in comparison to control.6. The results suggest: (a) endogenous nitric oxide is involved in regulation of coronary circulation by producing a basal vasodilator tone, (b) acetylcholine-induced coronary vasodilatation is mediated, in part, by nitric oxide, and (c) inhibition of basal endogenous nitric oxide production induces supersensitivity of coronary vessels to nitrovasodilators and enhances hyperaemic responses after short periods of ischaemia of the myocardium.
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PMID:Effects of nitric oxide synthesis inhibition on the goat coronary circulation under basal conditions and after vasodilator stimulation. 150 40

1. The role of endothelial nitric oxide synthesis from L-arginine in the regulation of coronary vascular tone and myocardial tissue perfusion was evaluated in anaesthetized, open-chest dogs. Coronary blood flow was measured with an electromagnetic flow probe placed around the left circumflex coronary artery. Coronary vascular resistance was calculated from mean arterial blood pressure and mean coronary blood flow, whereas regional myocardial tissue flow was determined by use of the radioactive microspheres technique. 2. NG-monomethyl L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), administered directly into the left circumflex artery, induced a small increase in arterial blood pressure and an increase in coronary vascular resistance. However, myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural), was unaffected by L-NMMA or L-NAME. 3. Acetylcholine, administered intracoronarily, induced an increase in left circumflex coronary blood flow and a decrease in coronary vascular resistance, without affecting systemic haemodynamics. This coronary vasodilator effect of acetylcholine was markedly inhibited by L-NMMA and L-NAME, the latter being a more potent antagonist than the former. 4. These results indicate that the endothelial L-arginine pathway is largely responsible for the coronary vasodilator effect of acetylcholine. However, although basal release of nitric oxide from L-arginine apparently contributes to the regulation of resting coronary vascular tone, blockade of this pathway does not affect myocardial tissue perfusion, possibly because of compensatory mechanisms occurring at the level of small arterioles and/or capillaries.
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PMID:Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open-chest dogs. 178 19

1. An isolated, buffer-perfused rabbit ear preparation was used to investigate the influence of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodiltation and modulation of vasoconstrictor responses and vascular conductance. 2. Acetylcholine (0.55 pmol-1.6 nmol) caused dose-related vasodilatation of preparations constricted by the combination of 5-hydroxytryptamine and histamine (both 1 microM), with an ED50 = 31.1 +/- 7.8 pmol and a maximum dilatation of 69.9 +/- 4.3%. In the presence of 10 microM L-NAME the dose-response for vasodilator effects was shifted significantly (P less than 0.001) to the right (ED50 = 3.07 +/- 1.18 nmol) and there was a significant (P less than 0.01) depression of the maximum response (Rmax = 44.3 +/- 4.0%). The higher concentration of 100 microM L-NAME completely abolished vasodilatation to acetylcholine. L-Arginine (10 mM) did not reverse the inhibitory actions of L-NAME at either concentration. 3. L-NAME 100 microM, augmented vascular tone induced by 1 microM 5-hydroxytryptamine and 1 microM histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration-dependent manner by L-arginine (10 microM-10 mM) and the effect of L-NAME on the conductance/flow relationships was similarly reversed by 10 mM L-arginine. The augmentation of tone was endothelium-dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150s. 4. In conclusion, L-NAME is a potent inhibitor of agonist-induced endothelium-dependent vasodilatation. L-NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of L-arginine to reverse L-NAME-induced inhibition of basal EDRF activity but not L-NAME-induced inhibition of agonistinduced endothelium-dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of L-arginine to EDRF.
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PMID:Differential effects of L-arginine on the inhibition by NG-nitro-L-arginine methyl ester of basal and agonist-stimulated EDRF activity. 179 35

1. Conscious, Long Evans rats (n = 16), chronically instrumented for the measurement of regional haemodynamics were given 3 min, randomized infusions of two doses of sodium nitroprusside (1.5 and 15 micrograms min-1), acetylcholine (0.4 and 4 micrograms min-1), 5'-N-ethylcarboxamidoadenosine (NECA; 45 and 450 ng min-1), and salbutamol (24 and 240 ng min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 mg kg-1 h-1), a potent inhibitor of nitric oxide biosynthesis. 2. Sodium nitroprusside caused hyperaemic vasodilatation in the mesenteric, and common carotid vascular beds. These effects were enhanced in the presence of L-NAME, as was the hypotension. 3. Acetylcholine caused hyperaemic vasodilation inp6he renal, internal carotid and common carotid vascular beds. These effects were attenuated in the presence of L-NAME, but the hypotension was unaffected. 4. NECA caused hyperaemic vasodiltation in the renal, mesenteric, hindquarters, internal carotid and common carotid vascular beds. However, only the hindquarters and internal carotid responses were diminished in the presence of L-NAME and the hypotension was unchanged. 5. Salbutamol caused hyperaemic vasodilatation in the hindquarters vascular bed only. This effect was reduced in the presence of L-NAME, but the hypotension was unchanged. 6. The results indicate marked regional variations in the sensitivity of vasodilator responses to L-NAME that can depend on the vasodilator agent chosen and the dose employed. It is clear from these findings also that measurement of mean arterial blood pressure alone cannot provide adequate information on which to judge the involvement of L-NAME-sensitive mechanisms in vasodilator responses in vivo.
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PMID:Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats. 193 36

We examined the role of nitric oxide in the maintenance of coronary vascular tone in 15 dogs. A 0.014 inch Doppler wire was introduced into the midsegment of the circumflex coronary artery and a 4.3F, 30 MHz two-dimensional ultrasound imaging catheter was introduced over the Doppler wire. Acetylcholine caused a dose-dependent vasodilation in both epicardial and resistance coronary arteries. However, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthetase caused a dose-dependent vasoconstriction mainly in the epicardial coronary arteries, partially reversed by L-arginine. The vasodilator response to acetylcholine was inhibited by L-NAME only in the epicardial circulation. Thus using combined intracoronary two-dimensional and Doppler ultrasound, we have demonstrated both basal and acetylcholine-induced release of nitric oxide in epicardial coronary arteries. The failure of L-NAME to decrease basal and acetylcholine-induced increases in flow velocity suggests that endothelium-dependent relaxation in coronary resistance vessels may not be mediated by nitric oxide alone.
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PMID:Differential contribution of nitric oxide to regulation of vascular tone in coronary conductance and resistance arteries: intravascular ultrasound studies. 751 9

The sensitivity of rat cremaster muscle arterioles to topically applied arginine vasopressin (AVP) is greatly increased by endotoxin (ENDT) [1]. The hypothesis is that the increase in vasoconstrictor sensitivity is in part due to modification of the AVP responses by endothelial compounds such as nitric oxide (NO) and endothelin. Reactivity of left cremaster muscle microvessels of pentobarbital anesthetized Sprague-Dawley rats was measured using videomicroscopy. Femoral arterial pressure as well as second and third order arteriolar (A2 and A3) vasoconstrictor threshold responses were determined for topical AVP (10(-15)-10(-6) M). These measurements were repeated in the presence of ENDT (6 mg/kg) alone and in the presence of the NO synthase inhibitor L-NAME (N omega-nitro-L-arginine methyl ester; 1 mg/kg) and ENDT (group 1). The control threshold (M)(-log) for arteriolar constriction by AVP was 9.4 +/- 0.7. After ENDT the threshold decreased significantly (P < 0.05) to 13.8 +/- 0.5, but returned to 9.0 +/- 0.5 after i.v. injected L-NAME. Acetylcholine (ACh) injected i.a. during AVP constriction significantly increased diameters at control and after ENDT, but not after L-NAME. In group 2 the AVP threshold was determined at control, after L-NAME plus hydroquinone (HQ), and at 30, 90, and 120 min post-ENDT in the presence of L-NAME + HQ. The AVP threshold at control was 9.0 +/- 0.3, after L-NAME 9.0 +/- 0.6, and after HQ 8.0 +/- 0.7. After L-NAME + HQ, the threshold was significantly increased to 7.3 +/- 0.2. After ENDT, in the presence of both antagonists, the threshold remained elevated at 7.4 +/- 0.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modification of vasopressin microvascular responses by endotoxin, endothelin, and nitric oxide. 751 25

Careful handling and preparation of freshly harvested vessels from 22 pigs and 12 rabbits revealed a two-phase vasorelaxation response to cumulative doses of substance P (SP). A rapid, transient relaxation was observed during the cumulative dose-response and a new plateau of equilibrium was seen following an increase in developed force after the last dose of SP. The phase 2 response is also produced by submaximal doses of SP and is not altered by pretreatment of the rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L-NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a shift to the right in the phase 1 response to SP and a complete blockade of phase 2. Methylene blue caused nearly complete block of both phases. Nitroglycerin caused a dose-dependent and prolonged vasorelaxation with no phase 2.
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PMID:Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit carotid arteries. 752 May 54

1. We have examined the effects of nitric oxide inhibition, indomethacin and the dual lipoxygenase/cyclo-oxygenase inhibitor, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of small mesenteric arteries. Indomethacin (14 microM) attenuated the contractile response to both noradrenaline and potassium chloride. The inhibitory action of indomethacin persisted in vessels treated with CHAPS. 3. Acetylcholine produced concentration-dependent relaxation in these vessels. Indomethacin (14 microM) had no significant effect on the acetylcholine concentration-response relationship. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) potentiated the contractile response to both noradrenaline and potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5. BW755C inhibited the contractile response to noradrenaline and potassium chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in the presence of indomethacin and in vessels treated with CHAPS. 6. BW755C enhanced endothelium-dependent relaxation, as assessed by the response to acetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7. Inhibition of nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on noradrenaline- and potassium-induced contraction. L-NAME and BW755C in combination resulted in a shift to the right of the concentration-response curve to acetylcholine. 8. Sodium nitroprusside produced concentration-dependent relaxation of the vessels. Endothelium removal reduced the maximum relaxation to nitroprusside. BW755C did not alter the response to sodium nitroprusside in vessels with or without endothelium.9 .These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which appear to be largely endothelium-independent.
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PMID:Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid. 752 Dec 54

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)
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PMID:Activity of the L-arginine/nitric oxide pathway and endothelin-1 in experimental heart failure. 752 83

1. The roles of the tissue kallikrein-kinin system and nitric oxide (NO) release in Phoneutria nigriventer venom-induced relaxations of rabbit corpus cavernosum (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2. Phoneutria nigriventer venom (10-30 micrograms), porcine pancreatic kallikrein (100 mu), rabbit urinary kallikrein (10 mu), bradykinin (BK, 0.3-3 nmol), acetylcholine (ACh, 0.3-30 nmol) and glyceryl trinitrate (GTN, 0.5-10 nmol) caused relaxations of the RbCC strips. Captopril (1 microM) substantially potentiated Phoneutria nigriventer venom- and BK-induced RbCC relaxations without affecting those elicited by GTN. 3. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3,Thi5,D- Tic7,Oic8]-BK, 50 nM), aprotinin (10 micrograms ml-1) and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val- Gln-NH2 (KIZD-06, 1.3 microM) significantly inhibited Phoneutria nigriventer venom-induced RbCC relaxations, without affecting those provoked by GTN and ACh. The B1 receptor antagonist, [Leu9]des Arg10BK (0.5 microM) and soybean trypsin inhibitor (SBTI, 10 micrograms ml-1) had no effect on Phoneutria nigriventer venom-induced RbCC relaxations. 4. The relaxations induced by Phoneutria nigriventer venom, porcine pancreas kallikrein, BK and ACh were significantly inhibited by N omega-nitro-L-arginine methyl ester (L-NAME, 10 microM) but not by D-NAME (10 microM). L-NAME did not affect GTN-induced relaxations. L-Arginine (300 microM), but not D-arginine (300 microM), significantly reversed the inhibitory effect of L-NAME. 5. Our results indicate that Phoneutria nigriventer venom activates the tissue kallikrein-kininogen-kinin system in RbCC strips leading to NO release and suggest a functional role for this system in penile erection.
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PMID:Pharmacological characterization of rabbit corpus cavernosum relaxation mediated by the tissue kallikrein-kinin system. 752 16


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