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 investigated whether nitric oxide (NO) contributes to glomerular hyperfiltration in experimental diabetes. Thirty-five adult male Munich-Wistar streptozocin-diabetic rats and 39 nondiabetic controls were distributed among 4 groups: C, normal control; C + L-NAME, controls receiving the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 40 mg/dl in drinking water; DM, diabetic rats; DM + L-NAME, diabetic rats receiving L-NAME, 15 mg/dl in drinking water. After 1 month of treatment, the DM + L-NAME group exhibited renal vasoconstriction and lacked hyperfiltration. Acute administration of L-NAME, 2.5 mg/kg, depressed the glomerular filtration rate and promoted renal vasoconstriction to a much greater extent in the DM than in the C group. Acute administration of endothelin 1 (600 ng/kg, bolus) or angiotensin II (25 micrograms/kg/min, continuous infusion) exerted similar hemodynamic effects in the C and DM groups, suggesting that the enhanced response of DM to L-NAME reflected specific sensitivity to NO inhibition. Urinary excretion of nitrites and nitrates was fourfold higher in DM compared to C. These results support the notion that augmented NO production may contribute to renal hyperfiltration and hyperperfusion in diabetes.
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PMID:Renal effects of acute and chronic nitric oxide inhibition in experimental diabetes. 888 32

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.
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PMID:Chronic inhibition of nitric oxide synthase in Heymann nephritis. 888 33

The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on the in vivo eosinophil migration induced by bradykinin, platelet-activating factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and zymosan-activated serum was also evaluated in the rat. The eosinophils were obtained from the peritoneal cavity of male Wistar rats and isolated on a discontinuous metrizamide gradient. Chronic inhibition of nitric oxide biosynthesis was achieved by adding L-NAME to the drinking water to give an intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P < 0.01) compared with animals which received either the same dose of the inactive enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram), lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into untreated rats in vivo induced a significant level of eosinophil migration by 24 h post-injection. This migration was markedly reduced in L-NAME-treated rats. Eosinophils obtained from untreated rats showed a significant level of migration in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated serum (27 microliters). In contrast, the migration induced by these chemotactic agents was markedly reduced in cells isolated from animals treated chronically with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the ability of eosinophils from L-NAME-treated animals to migrate in response to fMLP. Our results indicate that nitric oxide plays a major role in the in vivo and ex vivo migration of eosinophils.
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PMID:Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis. 888 18

In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/kg.day of oral N-nitro-L-arginine methylester (L-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received L-NAME. Portal vein stenosed rats that received L-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 +/- 0.5 versus 3.7 +/- 0.2 ml/min.100 g and 96 +/- 1 versus 68 +/- 5%, respectively) and higher hepatocollateral vascular resistance (147 +/- 10 versus 295 +/- 30 dyn.s.cm-5.100 g.10(3), respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after L-NAME than after placebo. Normal rats had similar but less marked L-NAME-induced responses than portal hypertensive rats. The presence of a long-term L-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.
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PMID:Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension. 889 79

The role of brain L-arginine/nitric oxide biochemical pathway in the regulation of drinking behaviour was investigated. Drinking was induced by water deprivation or by intracerebroventricularly (i.c.v.) injected angiotensin II. L-Arginine, the amino-acid precursor of nitric oxide, i.c.v. injected, caused a dose-dependent reduction of the intake of water induced both by water deprivation and i.c.v. angiotensin II (P < 0.001). L-NAME, inhibitor of nitric oxide synthase, reverted L-arginine antidipsogenic effect. L-Arginine, given into the preoptic area (POA) caused a potent antidipsogenic effect (P < 0.001). Either methylene blue (inhibitor of guanylate cyclase activation) or acetylsalicylic acid (ASA), injected into the POA, antagonized the antidipsogenic effect of i.c.v. injected L-arginine. The results indicate that nitric oxide acts as an inhibitory mechanism into the POA and that its antidipsogenic effect requires prostaglandin synthesis.
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PMID:Nitric oxide and drinking behaviour. 889 5

In the present study we evaluated the effects of methimazole, an antithyroid drug, on blood pressure and other variables in the early and established phases of hypertension induced by the inhibition of nitric oxide synthesis with the oral administration of NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking water. Moreover, we also evaluated the acute pressor effect of L-NAME on systemic blood pressure in control and rats treated chronically with methimazole, administered via drinking water (30 mg/100 ml). Oral administration of methimazole maintained the blood pressure of L-NAME-treated rats at normal levels 25 days after induction of hypertension. However, after 25 days of methimazole treatment in rats made hypertensive with L-NAME (for 25 days), high blood pressure was similar in methimazole-treated and non-treated L-NAME rats, despite the fact that a hypothyroid state had been achieved in the methimazole-treated rats. Acute intravenous injection of L-NAME caused a similar increase in mean arterial pressure in control and methimazole-treated rats at the lowest dose; however, smaller pressor responses were observed with increasing doses in hypothyroid rats. These results clearly demonstrate that hypothyroidism induced by methimazole prevents, but does not reverse, L-NAME hypertension and reduces the acute pressor responsiveness to L-NAME administration.
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PMID:Effects of methimazole in the early and established phases of NG-nitro-L-arginine methyl ester hypertension. 892 35

The pulmonary vascular responses to changes in perfusate viscosity were studied in isolated rat lungs treated with the nitric oxide synthase (NOS) inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) and N omega- monomethyl-L-arginine (L-NMMA). Lungs were isolated according to standard protocols and perfused with varying concentrations of albumin in physiological salt solution (PSS) and with low, intermediate, and normal hematocrits using washed erythrocytes. Pressure-flow curves were generated by increasing pulmonary arterial pressure (PPA) while keeping pulmonary venous pressure (PPV) constant and measuring flow at each pressure interval. Neither perfusate flow nor pulmonary vascular resistance changed after L-NAME or L-NMMA (300 microM) at any pressure interval in lungs perfused with 4 and 10% albumin/PSS. In lungs perfused with 20% albumin/PSS, L-NMMA decreased flow at all PPA tested except 10 cm H2O (P < 0.05). L-NAME decreased flow in lungs perfused with normal (39.2 +/- 2.1%) hematocrits at all PPA tested. Conversely, L-NAME decreased flow in lungs perfused with low and intermediate hematocrits only at the highest pressure intervals. L-Arginine, when given after NOS inhibitors, failed to restore flow to baseline values in any group of lungs. N omega-nitro-D-arginine methyl ester (300 microM) did not change flow at any pressure interval in lungs perfused with normal (43 +/- 1.5%) hematocrit, washed erythrocytes. We conclude that lungs perfused with intermediate and normal hematocrit, washed erythrocytes, as well as with high-viscosity albumin/PSS solutions, show increased pulmonary vascular responses to NOS inhibitors.
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PMID:Perfusate viscosity and hematocrit determine pulmonary vascular responsiveness to NO synthase inhibitors. 892 83

We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important.
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PMID:Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. 894 32

We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) for 4 wk caused hypertension and a significant reduction in urinary NO2- and NO3- excretion. Four-week oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter blood pressure but caused a significant decrease in urinary NO2- and NO3-. Rats treated with L-NAME at doses of 20 and 50 mg/dl had normal bone mineral mass in the lumbar spine, but the highest dose (80 mg/dl) caused a slight decrease in bone mass. Chronic AG induced a significant spine osteopenia. This effect of AG was abolished by the simultaneous administration of L-arginine (2.0 g/dl). AG-induced osteopenia was associated with a significant increase in urine excretion of collagen cross-links with normal serum osteocalcin. These findings indicate that chronic AG administration can cause an imbalance between bone resorption and formation, resulting in a decrease in bone mass in growing rats, and suggest that NO produced by inducible NO synthase plays an important role in basal osteoclast bone degradation activity in vivo.
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PMID:Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats. 896 73

Exposure to high oxygen concentration leads to acute lung injury and death in rats after 72 h. The pathophysiology of this phenomenon relies on several mechanisms, including alteration of vascular reactivity, recruitment and activation of neutrophils and alveolar macrophages, production of cytokines and excess production of free radicals. In addition to its potent vasodilating effect, nitric oxide (NO) has also been reported to prevent free radical-mediated damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to continuous high oxygen concentration, we studied the effect of administration of 50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to oxygen and injected with L-NAME died within 60 h as compared to 22% of the animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and bronchoalveolar lavage fluid protein were also significantly increased in animals exposed to oxygen and receiving L-NAME. The lung water content was higher in the oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05). Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p < 0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a deleterious effect in rats exposed to hyperoxia, which might suggest that endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary lesions.
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PMID:L-NAME aggravates pulmonary oxygen toxicity in rats. 898 Sep 65


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