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)

1. The ability of nitric oxide inhibitors to antagonize the febrile effects of lipopolysaccharide (LPS) endotoxin (20 microg/animal i.v.) was assessed in prepubertal pigs in which deep body temperature was measured at 10-min intervals for 180 min. 2. In experiment 1, pigs (n=5) were injected with Nomega-nitro-L-arginine-methyl ester (L-NAME) (30 mg/kg i.v.) or aminoguanidine (27 mg/kg i.v.) 30 min before LPS. There was a marked tendency for L-NAME, but not aminoguanidine, to reduce LPS pyrexia. 3. In experiment 2, pigs (n=7) were injected with 2-amino-4-methylpyridine (1 mg/kg i.v.) 30 min before LPS. This drug tended to increase, rather than reduce, core temperature. 4. In experiment 3, pigs (n=5) were injected with S-methylisothiourea (10 or 15 mg/kg i.v.) concomitantly with LPS. Both doses of the drug produced a small, nonsignificant, reduction in the febrile response. 5. The results indicate that the nitric oxide inhibitors used in this study were relatively ineffective in modifying LPS fever in conscious pigs; these findings are in marked contrast with the actions, in this species, of drugs that inhibit prostaglandin production. In addition, the most effective drug, L-NAME, was the one considered to be the least selective for the inducible form of nitric oxide.
Gen Pharmacol 1998 Sep
PMID:Effects of intravenous nitric oxide inhibitors on endotoxin-induced fever in prepubertal pigs. 970 4

The present study was designed to determine the role of endogenous endothelin peptides and nitric oxide on angiotensin II (All) responses in the isolated nonpregnant rat uterine smooth muscle. AII (10, 20, or 50 ng/ml) increases rhythmic oscillations dose dependently (32.7 +/- 8.9, 55.96 +/- 10.3, and 62.78 +/- 17.7% increase, respectively). L-arginine methyl ester (L-NAME; 10(-5) M) did not affect the increase in rhythmic oscillations induced by All (10, 20, or 50 ng/ml) (17.5 +/- 12.1, 31.5 +/- 18.3, and 52.5 +/-11.8% increase, respectively, n = 6, p > 0.05). It reduced the contractile responses to AII (10 ng/ml: from 4.63 +/- 0.6 to 1.8 +/-0.7 cm2, p < 0.05: and 20 ng/ml: from 5.59 +/- 0.8 to 2.11 +/- 0.4 cm2, p < 0.05, n = 6). L-arginine (10 mM) decreased the contractile response obtained by AII (10 or 20 ng/ml) (1.93 +/- 1.05, p < 0.05 and 2.14 +/- 0.7 cm2, p < 0.05, respectively, n = 6). BQ 485 (50 ng/ml) decreased both the number of rhythmic oscillations and the contractility increased by AII. Bosentan (10(-5) M) induced an increase in the number of rhythmic oscillations but decreased the contractile responses to the higher concentrations of All. These data show that endogenous NO and endothelin peptides contribute to the motility changes induced by AII and may play an important role in the pathophysiological events of the uterine function.
Gen Pharmacol 1999 Oct
PMID:The contribution of nitric oxide and endothelins to angiotensin: II. Evoked responses in the rat isolated uterus smooth muscle. 1052 68

In phenylephrine-precontracted rings, H2O2 produced an endothelium-dependent relaxation at concentrations of 4.4 x 10(-7) to approximately 4.4 x 10(-5) M. Removal of extracellular Ca2+ ([Ca2+]0) markedly attenuated the relaxant effects of H2O2. Complete inhibition of the H2O2 relaxant action was obtained after buffering intracellular Ca2+ ([Ca2+]i) in endothelial cells, with 10 microM acetyl methyl ester of bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). These relaxant effects of H2O2 were nearly abolished by 15 x 10(-5)M N(G)-monomethyl-arginine (L-NMMA) or 5 x 10(-5) M N(G)-nitro-L-arginine (L-NAME) and were attenuated markedly by the presence of either 10(-6) M Fe2+, 10(-6) M Fe3+, or 5 x 10(-6) M methylene blue. These inhibitory effects of L-NMMA or L-NAME could be reversed partly by 5 x 10(-5) M L-arginine. These Fe(2+)- and Fe(3+)-induced inhibitions of H2O2-stimulated relaxation were reduced significantly by either 1.0 mM deferoxamine (a Fe2+ chelator) or 100 microM dimethyl sulfoxide (DMSO). In addition, 17-octadecynoic acid (2.5 microM) or proadifen (10 microM) (both antagonists of cytochrome P450 metabolism of fatty acids) markedly decreased the H2O2 relaxant effects. Proadifen (10 microM) produced concentration-dependent impairment of vasorelaxation to acetylcholine. A variety of amine antagonists and a cyclo-oxygenase inhibitor all fail to interfere with or attenuate the H2O2-induced relaxations. Our observations suggest that, at suitable pathophysiologic concentrations, H2O2 could induce release of an endothelium-derived relaxing factor, probably nitric oxide, from endothelial cells. The H2O2 relaxant effects are clearly Ca(2+)-dependent and require formation of cyclic guanosine monophosphate (cGMP). These vasorelaxing effects of H2O2 appear to be induced by H2O2 itself. Hydrogen peroxide may stimulate production of some unknown metabolites metabolized by cytochrome P450-dependent enzymes.
Gen Pharmacol 1999 Oct
PMID:Hydrogen peroxide-induced endothelium-dependent relaxation of rat aorta involvement of Ca2+ and other cellular metabolites. 1052 71

N(G)-nitro-D-arginine methyl ester (D-NAME), considered as an inactive enantiomer of NAME, is generally used as a negative control for NO synthase inhibition with L-NAME. The aim of this work was to compare the effect of L-NAME (20 and 40 mg/kg/day), and D-NAME (40 mg/kg/day) on hemodynamic and structural parameters in the rat cardiovascular system. After 4 weeks of treatment, blood pressure and left ventricle weight/body weight ratio increased significantly in all studied groups versus control. Myocardial fibrosis (in %) represented 0.94 +/- 0.04 in control, 4.70 +/- 0.39 in L-NAME (20 mg/kg/day), 10.54 +/- 0.91 in L-NAME (40 mg/kg/day) and 5.25 +/- 0.46 in D-NAME (40 mg/kg/day) group. We conclude that in a long-term experiment D-NAME provokes similar changes in cardiovascular system like L-NAME.
Gen Physiol Biophys 1999 Dec
PMID:Structural alterations in the heart after long-term L-NAME and D-NAME treatment. 1070 23

(Na,K)-ATPase, an enzyme involved in the active translocation of Na+ and K+ ions across cell membranes was shown to be affected by nitric oxide (NO) in various tissues. In the present study the functional alterations of (Na,K)-ATPase after chronic inhibition of nitric oxide synthesis were studied in rat hearts. Four weeks lasting administration of an L-arginine analogue, the N(G)-nitro-L-arginine methyl ester (L-NAME) induced an increase in the systolic blood pressure of about 36%. In this hypertension the kinetic parameters Km and Vmax for ATP-activation of the (Na,K)-ATPase did not show any significant changes. Activation of the enzyme by its cofactor Na+ revealed no change in the Vmax, but the K(Na) increased by 50%. Two weeks after terminating the administration of L-NAME the blood pressure returned to control values. In these conditions the activity of (Na,K)-ATPase increased, due to enlarged affinity of the ATP-binding site as revealed from the diminished Km value for ATP. The K(Na) value for activation with Na+ returned to control value. Our findings indicate that there is no change in energy utilization by the (Na,K)-ATPase during L-NAME induced hypertension in the heart. The transport properties of the enzyme are deteriorated, due to its decreased sensitivity to Na+. This inhibition of the (Na,K)-ATPase might be responsible for the increase of [Na+]i during lowered NO synthesis. In hearts from rats that recovered from the hypertension, the (Na,K)-ATPase increases its activity due to improved ATP binding properties.
Gen Physiol Biophys 1999 Dec
PMID:Functional alterations of cardiac (Na,K)-ATPase in L-NAME induced hypertension. 1070 24

This study deals with qualitative alterations of membranes in cardiac cells after chronic inhibition of NO synthesis in rats induced by administration of N(G)-nitro-L-arginine methyl ester (L-NAME) in a dose 40 mg/kg/day for 4 weeks. Concentration of proteins did not change either in the cytosolic fraction or in the particulate fraction of the cardiac homogenate from L-NAME treated rats. The concentration of phospholipids and consequently the ratio of phospholipids to membrane proteins increased by 100% and 88%, respectively. The concentration of conjugated dienes (CD), often used as an indirect marker for the production of free oxygen radicals, increased by 141% after calculation per gram of tissue. However, evaluation of CD concentration directly in phospholipids revealed no change, suggesting that phospholipids in cardiac tissue after L-NAME treatment were not damaged additionally, by increased level of free oxygen radicals. The increase of the CD concentration in the cardiac tissue is therefore, a consequence of the elevated phospholipid concentration.
Gen Physiol Biophys 1999 Dec
PMID:Cardiac membrane proteins and phospholipids in L-NAME induced hypertension. 1070 25

We examined the role of the nitric oxide (NO) pathway on ischemia-reperfusion injury with the use of isolated perfused guinea pig hearts. We administered to the heart either L-arginine or N-nitro-L-arginine methyl ester (L-NAME) before or after 20 min of ischemia, and we observed the heart rate, aortic pressure, and contractile force, as well as the levels of malondialdehyde (MDA) and glutathione (GSH). We observed that L-NAME increased the tissue MDA levels and aortic pressure. On the other hand, L-arginine before the onset of reperfusion decreased aortic pressure and tissue MDA levels but increased the tissue GSH levels. We concluded that L-arginine administration before the onset of reperfusion improves myocardial recovery from ischemic injury.
Gen Pharmacol 2000 Jan
PMID:Role of the nitric oxide pathway on ischemia-reperfusion injury in an isolated perfused guinea pig heart. 1079 62

We have used the patch-clamp technique to study the effects of changing extracellular ATP concentration on the activity of the small-conductance potassium channel (SK) on the apical membrane of the mouse cortical collecting duct. In cell-attached patches, the channel conductance and kinetics were similar to its rat homologue. Addition of ATP to the bathing solution of split-open single cortical collecting ducts inhibited SK activity. The inhibition of the channel by ATP was reversible, concentration dependent (K(i) = 64 microM), and could be completely prevented by pretreatment with suramin, a specific purinergic receptor (P(2)) blocker. Ranking of the inhibitory potency of several nucleotides showed strong inhibition by ATP, UTP, and ATP-gamma-S, whereas alpha, beta-Me ATP, and 2-Mes ATP failed to affect channel activity. This nucleotide sensitivity is consistent with P(2)Y(2) purinergic receptors mediating the inhibition of SK by ATP. Single channel analysis further demonstrated that the inhibitory effects of ATP could be elicited through activation of apical receptors. Moreover, the observation that fluoride mimicked the inhibitory action of ATP suggests the activation of G proteins during purinergic receptor stimulation. Channel inhibition by ATP was not affected by blocking phospholipase C and protein kinase C. However, whereas cAMP prevented channel blocking by ATP, blocking protein kinase A failed to abolish the inhibitory effects of ATP. The reduction of K channel activity by ATP could be prevented by okadaic acid, an inhibitor of protein phosphatases, and KT5823, an agent that blocks protein kinase G. Moreover, the effect of ATP was mimicked by cGMP and blocked by L-NAME (N(G)-nitro-l-arginine methyl ester). We conclude that the inhibitory effect of ATP on the apical K channel is mediated by stimulation of P(2)Y(2) receptors and results from increasing dephosphorylation by enhancing PKG-sensitive phosphatase activity.
J Gen Physiol 2000 Aug
PMID:Extracellular ATP inhibits the small-conductance K channel on the apical membrane of the cortical collecting duct from mouse kidney. 1091 72

Relaxations to acetylcholine and contractions to acetylcholine in the presence of the nitric oxide (NO) synthesis inhibitor (L-N(G)-nitroarginine methyl ester, L-NAME) were studied in aortic rings from rabbits fed either a control or a diet containing 0.5% cholesterol+14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg kg(-1) day(-1)). Rings were incubated with the endothelin (ET(A)) receptor antagonist BQ123, and/or the thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist ifetroban. In rabbits, high cholesterol and triglyceride plasma levels were associated with intimal thickening and blunted acetylcholine-relaxation as compared with controls. By contrast, acetylcholine+L-NAME response was higher. Incubation with either ifetroban or BQ123 increased acetylcholine-relaxation in both diet groups and it reduced the constrictor response only in dyslipidemic rabbits. Removal of endothelium reduced acetylcholine+L-NAME contraction in dyslipidemic rabbits, although increased it in control animals. Atorvastatin treatment reduced plasma lipid levels and lesion size in dyslipidemic animals. Likewise, it prevented acetylcholine-relaxation reduction. In addition, atorvastatin reduced constrictor response in dyslipidemic rabbits but only in rings with endothelium. Incubation with either ifetroban or BQ123 did not further modify these responses in atorvastatin-treated animals in any group. These data suggest that ET and TXA(2) availabilities seem to participate in the endothelial dysfunction associated with dyslipidemia. Atorvastatin treatment reduces intimal thickening and improves endothelial dysfunction in rabbits. This effect seems to be a consequence of its ability to act on ET and TXA(2) systems.
Gen Pharmacol 2000 Apr
PMID:Effect of atorvastatin on endothelium-dependent constrictor factors in dyslipidemic rabbits. 1128 20

The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide synthase inhibitor), and adrenaline on the contractile tone of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated. None of the neuropeptides, which had previously been found to be present in the aortic anastomosis, had any direct effect on the tension developed by ring preparations. L-NAME itself significantly increased the basal tone of the vascular ring preparations, suggesting a tonic release of nitric oxide in the preparation. Adrenaline produced concentration-dependent vasoconstrictions that were counteracted by profound reflex vasodilatations that were susceptible to blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide synthase and tyrosine hydroxylase-containing (indicating the presence of a adrenergic innervation) nerve fibres in the adventitia and adventitio-medial border of the aortic anastomosis. These data demonstrate opposing actions of adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of the C. porosus. The morphology of the anastomosis, with the extremely thick muscular vessel wall, suggests a sphincter-like function for this vessel that could be controlled mainly by adrenergic and nitrergic mechanisms.
Gen Comp Endocrinol 2001 May
PMID:Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus. 1131 25


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