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)

Fourteen mongrel dogs were chronically instrumented on the circumflex coronary artery for measurement of coronary diameter (CD; Piezoelectric crystals) and coronary blood flow (CBF: Doppler flow probe). Coronary resistance (CR) was calculated as mean arterial blood pressure (MAP)/CBF. Systemic and coronary effects of three intravenous doses of NG-nitro-L-arginine (L-NAME: 0.1; 0.3; 1 mg/kg) were recorded (n = 5). Systemic and coronary effects of two vasodilators, acetylcholine (ACH) (endothelium-dependent: 0.3 micrograms/kg) and nitroglycerin (NTG) (endothelium-independent: 1 microgram/kg) were compared before and after L-NAME (1 mg/kg) (n = 6). Finally, the effects of L-NAME (1 mg/kg) were compared one week before and three days after denudation (balloon catheter) of the circumflex coronary artery (2 cm up and downstream from the crystals attachment site). All experiments were performed in conscious dogs. L-NAME induced a dose-dependent constriction of large epicardial coronary arteries [-1.5 +/- 0.5% from 3.1 +/- 0.3 mm, p < 0.05; -4.0 +/- 0.7% from 3.2 mm, p < 0.001; -5.3 +/- 1.2% from 3.0 mm, p < 0.01; respectively]. L-NAME 0.3 and 1 mg/kg induced a significant increase in MAP [+12.5 +/- 3.0% from 90 +/- 4 mmHg, p < 0.01; +11.3 +/- 3.5% from 96 +/- 7 mmHg, p < 0.05; respectively] and CR [+18.0 +/- 8.3% from 9.8 +/- 3.0 mmHg/cm.s, p < 0.01; +18.7 +/- 8.2% from 10.4 +/- 3.0 mmHg/cm.s, p < 0.01; respectively] with a significant bradycardia, but CBF was not modified. Effects of ACH were unchanged after L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Systemic and coronary hemodynamic effects of inhibition of nitrogen monoxide synthesis in conscious dogs]. 148 63

Vasodilation following the infusion of acetylcholine is due to the release of endothelium-derived relaxing factor (EDRF). However, the role of EDRF in neurogenic coronary vasodilation, when acetylcholine is released outside the vessel at the adventitial-medial junction, has not been established. The action of EDRF in parasympathetic coronary vasodilation was tested in the present study using a specific inhibitor of EDRF synthesis, nitro-L-arginine methyl ester (L-NAME). Experiments were conducted on closed-chest, alpha-chloralose-anesthetized dogs with the heart paced at a constant rate. Phentolamine and propranolol were administered to block alpha- and beta-adrenergic receptors, and ibuprofen was given to inhibit prostaglandin synthesis. Intracoronary infusion of L-NAME decreased the coronary vasodilation in response to intracoronary acetylcholine or vagal stimulation. The coronary response to the endothelium-independent vasodilator nitroglycerin was unaffected by L-NAME. These data demonstrate that L-NAME specifically inhibits coronary vasodilation caused by acetylcholine and vagal stimulation, indicating that parasympathetic coronary vasodilation is dependent on EDRF.
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PMID:Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation. 159 Apr 63

Vascular endothelial cells synthesize nitric oxide from L-arginine, and this pathway can be inhibited by various analogues of L-arginine, including NG-nitro L-arginine methyl ester (L-NAME). To investigate the role of this pathway in the regulation of femoral arterial tone, the effect of L-NAME was studied in vitro in isolated canine femoral arteries suspended in organ chambers for isometric tension recording, and in vivo in conscious dogs chronically instrumented for the measurement of iliac blood flow and iliac artery diameter. In vitro, L-NAME induced an endothelium-dependent contraction, inhibited the endothelium-dependent relaxations to acetylcholine or bradykinin, and potentiated the relaxation evoked by the nitric oxide donor SIN-1. In vivo, locally administered L-NAME induced a decrease in iliac artery diameter and an increase in iliac resistance, potentiated the iliac responses to the organic nitrate nitroglycerin, but did not affect the iliac responses to the endothelium dependent vasodilator acetylcholine. Thus, in the canine femoral vascular bed: a) basal release of nitric oxide contributes in vivo to the maintenance of a permanent vasodilator tone at the level of both large conductance and small resistance vessels; b) the endothelium-dependent relaxations to acetylcholine and bradykinin in vitro are mostly mediated through the release of nitric oxide from L-arginine; c) the endothelium-dependent relaxations to acetylcholine in vivo are probably mediated by a relaxing factor distinct from nitric oxide, or by a nitric oxide-like molecule released from endothelial pools; and d) removal of the NO-mediated vasodilator tone by L-NAME leads to a supersensitivity to nitrovasodilators, both in vitro and in vivo.
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PMID:The L-arginine-nitric oxide pathway in the canine femoral vascular bed: in vitro and in vivo experiments. 179 33

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

Aging is an important risk factor for impotence in men. Because nitric oxide (NO) appears to be the mediator of corpora cavernosal smooth muscle relaxation, we have examined in 5-, 20-, and 30-mo-old rats, designated "adult," "old," and "senescent," respectively, whether aging causes a decrease of erectile response that may correlate with lower NO synthase (NOS) in the penis. Electric field stimulation (EFS) of the cavernosal nerve showed that the maximum intracavernosal pressure (MIP) declined in the old and senescent rats to 80 and 51% of the adult value, respectively. A low systemic dose of the NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME; 2 mg/kg), reduced the MIP by only 38% in the adult rats but decreased it in the old and senescent rats by 72 and 80%, respectively. In the absence of EFS, intracavernosal papaverine (phosphodiesterase inhibitor), or nitroglycerin (NO donor), caused a lower erectile response in the old and senescent rats compared with the adult animals (MIP: 41 and 14%, respectively; duration of the erection 46 and 21%, respectively). Tissue sections from old and senescent penises showed increasing degrees of sclerotic degeneration. In comparison with the adult rats, the penile soluble NOS activity per gram of tissue that is sensitive to L-NAME decreased significantly by 63% in the senescent rats but was elevated in the old rats. These results indicate that aging causes an erectile failure due to factors initially independent from an impairment of penile NO synthesis but which are compounded in the very old rats by the decrease of penile NOS activity.
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PMID:Effect of aging on nitric oxide-mediated penile erection in rats. 753 Sep 24

Direct evidence for in vivo NO formation from nitroglycerin (GTN) was obtained by measurements of exhaled nitric oxide in anaesthetized. Infusions of GTN (1-100 micrograms kg-1 min-1 i.v.) induced dose-dependent and biphasic increments in exhaled NO parallelled by reductions in systemic blood pressure. The NO detected during GTN infusion was unaffected by the nitric oxide synthase inhibitor L-NAME or acute i.v. administration of L-cysteine, N-acetyl-L-cysteine or glutathione. The present data demonstrate that NO is formed from GTN in vivo, and that tolerance in vivo is due to decreased formation of NO.
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PMID:Rapid tolerance to formation of authentic NO from nitroglycerin in vivo. 771 83

A long-term study to identify age-dependent alterations in vascular reactivity in obese Zucker rats, a model for non-insulin-dependent diabetes mellitus, was carried out. On aortic rings of 12-week-old obese Zucker rats, but not in older animals (36 and 52 weeks), the following different effects in comparison to the lean rat control group were observed: (i) a significantly enhanced maximal relaxation to acetylcholine and A23187, which was abolished by the nitric oxide-synthase inhibitor L-nitro-arginine methyl ester (L-NAME); relaxation of aortic rings to the endothelium-independent vasodilator nitroglycerin was similar; (ii) more pronounced maximal 5-hydroxytryptamine-induced-contractions in the presence of L-NAME, and (iii) a more pronounced reduction in phenylephrine-induced contractions by verapamil. These results are suggestive of an altered calcium metabolism in the first weeks of development in the obese rat strain, which is probably responsible for the hypotension seen in this early time period.
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PMID:Age-related changes in vascular reactivity in genetically diabetic rats. 779 11

The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L-arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control.
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PMID:Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius. 786 45

The purpose of this study was to determine whether suffusion of L-arginine alone induces vasodilation in the cheek pouch of hamsters with hereditary cardiomyopathy in comparison with controls, and whether these effects are mediated by the L-arginine/nitric oxide biosynthetic pathway. Using intravital microscopy, we found that suffusion of L-arginine for 20 minutes induced a significant, stereospecific concentration-dependent vasodilation in hamsters with hereditary cardiomyopathy but not in controls (p < 0.05). These responses were abrogated by suffusion of the nitric synthase inhibitor NG-L-arginine methyl ester (L-NAME) but not by suffusion of D-NAME. Suffusion of nitroglycerin, a nitric oxide donor, induced significant vasodilation of similar magnitude in both groups (p < 0.05). L-NAME had no significant effects on nitroglycerin-induced responses in both groups. We conclude that direct application of L-arginine alone to the peripheral microcirculation in cardiomyopathy induces significant vasodilation that is mediated, most likely, via a nitric oxide-dependent mechanisms(s). We suggest that a reversible, L-arginine-responsive impairment in the constitutive L-arginine/nitric oxide biosynthetic pathway is present in the peripheral microcirculation in cardiomyopathy.
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PMID:L-arginine dilates cheek pouch arterioles in hamsters with hereditary cardiomyopathy but not in controls. 789 97

Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodilator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate the pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis in rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end-products of NO) by 4.3-fold. Rats given 10 micrograms/kg/hr i.v. of nitroglycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME, an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS-treated rats but not in rats given GTN. Glomerular thrombosis developed in rats given LPS + L-NAME (thrombosis score = 3.02 +/- 0.4), while those given LPS + L-NAME + GTN were largely protected (thrombosis score = 1.37 +/- 0.5, P < 0.05). Atrial natriuretic peptide (ANP), an NO-independent vasodilator, neither increased urinary NO2 + NO3 nor prevented glomerular thrombosis (thrombosis score = 2.68 +/- 0.5, NS). Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME. We conclude that in endotoxemia, the antithrombogenic properties of endogenously synthesized NO are important in preventing alomerular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be combined with concomitant administration of exogenous NO donors to prevent microvascular thrombosis.
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PMID:Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. 799 92


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