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)

The objective of this study was to assess the role that nitric oxide (NO) may play in mediating the colonic inflammation observed in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS). The NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME; 15 mumol/kg/day) and aminoguanidine (AG; 15 mumol/kg/day) were administered to rats in their drinking water, beginning 3 days before the induction of colitis and continuing for the entire 3-week period. We found that chronic NOS inhibition by L-NAME or AG significantly attenuated the peptidoglycan/polysacchride (PG/PS)-induced increases in macroscopic colonic inflammation scores and colonic MPO activity. Only AG, and not L-NAME, attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen inflammation, whereas neither drug significantly attenuated the PG/PS-induced liver inflammation. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG was found to attenuate these values significantly (38 +/- 3 vs. 83 +/- 8 microM, respectively; P < .05). Finally, administration of L-NAME, but not of AG, significantly increased mean arterial pressure from 83 mm Hg in colitic animals to 105 mm Hg in the PG/PS+L-NAME-treated animals (P < .05). We conclude that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.
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PMID:Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis. 752 37

1. L-Arginine elevates plasma insulin in man. Recent in vitro data indicate that this is based on stimulation of endogenous nitric oxide (NO) with subsequent pancreatic release of insulin by L-arginine. L-Arginine also raises plasma glucose. 2. We studied plasma levels of insulin, glucose and NO metabolites, as well as systemic blood pressure, in anaesthetized rats during i.v. infusion of L-arginine (25-200 mg kg-1 min-1) or glucose (55 mg kg-1 min-1), before and after administration of the NO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1). 3. Before L-NAME, L-arginine elevated plasma insulin from about 15 to 65 ul-1 and glucose from 5.2 to 6.7 mmol l-1. These effects of L-arginine were not dose-related. 4. L-NAME alone had no effect on plasma insulin and glucose levels, but diminished the effects of a low dose (25 mg kg-1 min-1) of L-arginine on plasma insulin by about 40%, and that on plasma glucose by more than 90%. In contrast, the effects of a high dose (200 mg kg-1 min-1) of L-arginine on plasma insulin and glucose levels were not affected by L-NAME. 5. L-NAME elevated systemic blood pressure by about 35 mmHg. L-Arginine (25-100 mg kg-1 min-1) had no effect on systemic blood pressure, either before or after L-NAME. L-Arginine (200 mg kg-1 min-1) lowered systemic blood pressure, both before and after L-NAME. 6. Glucose infusion elevated plasma glucose from about 5.5 to 6.8 mmol l-1, and plasma insulin from about 18 to 26 ul-1. 7. The basal plasma levels of the NO metabolite nitrate (18 +/- 4 mumol l-1) were not affected by L-arginine (200 mg kg-1 min-1). Plasma nitrosohaemoglobin was likewise unaffected by L-arginine (200 mg kg-1 min-1). 8. We conclude that L-arginine separately elevates plasma insulin and glucose levels, both by NO-dependent and -independent mechanisms.
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PMID:NO-dependent and -independent elevation of plasma levels of insulin and glucose in rats by L-arginine. 753 May 68

In this study, we have investigated the release of nitric oxide from resting human platelets. Nitric oxide was detected and quantitated by either measuring the conversion of oxy-hemoglobin to met-hemoglobin or generation of nitrite and nitrate by the cells. Nitric oxide was released from both intact resting platelets and platelets activated by collagen. Nitric oxide release was proportional to platelet concentration, and was equivalent to approximately 4.5 +/- 0.6 pmol (or 2.8 +/- 0.3 pmol in the presence of prostaglandin I2) and 11.2 +/- 1.3 pmol nitric oxide released per minute per 10(8) cells at 37 degrees C for resting platelets and platelets activated by collagen, respectively. The generation of nitric oxide by resting platelets was linear with respect to time over a two hour period, while the release of nitric oxide from platelets following activation was transient and was linear for only the first 10 min, after which it slowed to completion at approximately 30 min. The release of nitric oxide was it slowed to completion at approximately 30 min. The release of nitric oxide was stimulated by L-arginine, but was inhibited by L-nitro-arginine methyl ester (L-NAME). The inhibitory effect of L-NAME could be reversed by addition of L-arginine. The release of nitric oxide from platelets was also partially inhibited by prostaglandin I2, prostaglandin E1, aspirin and EDTA. The amount of nitric oxide released from resting platelets compared with that released from endothelial cells suggests that platelet-derived nitric oxide may play a significant role in the maintenance of vascular tone and blood flow.
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PMID:Nitric oxide release from resting human platelets. 770 81

To evaluate the role of nitric oxide (NO) in diabetic hyperfiltration, renal hemodynamic changes and changes in urinary excretion of NO2/NO3 in response to the NO inhibitor nitro-L-arginine methyl ester (L-NAME) and the NO-donating agent glyceryl trinitrate (GTN) were investigated in conscious streptozocin-induced diabetic (D) and age-matched control (C) rats. In all experiments, D rats demonstrated increased glomerular filtration rate (GFR), renal plasma flow (RPF), polyuria, and an increased urinary sodium excretion when compared with C rats. An intravenous bolus of low-dose L-NAME (1 mg/kg body wt) increased modestly systolic blood pressure (sBP) in C rats but had no effect on sBP in D rats. L-NAME induced a marked decrease in GFR and RPF in D rats with no change in filtration fraction (FF). In C rats, no change in GFR was observed, and RPF decreased, resulting in a rise in FF. A supramaximal dose of L-NAME (10 mg/kg body wt) increased sBP in C and D rats to a similar degree. With high-dose L-NAME, GFR decreased in D but not in C rats. There was a greater decrease in RPF in D rats when compared with C animals. An intravenous infusion of GTN induced a modest decrease in sBP in both C and D rats (P < 0.01). There were no changes in GFR and RPF in D rats, but in the C group, GTN increased RPF (P < 0.05) with a tendency for a rise in GFR (P = 0.09). Basal urinary NO2/NO3 excretion was increased in D rats in all experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes. 792 87

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

We examined potential mechanisms responsible for the parenchymal lung injury seen in an animal model of smoke inhalation with concurrent inflammation. Rats injected with sterile glycogen and exposed to smoke generated by the nonflaming pyrolysis of combined Douglas fir wood and polyvinylchloride showed a 74% increase in 125I-albumin lung permeability and a fivefold increase in lung myeloperoxidase (MPO) compared with control rats. There was also a significant increase in plasma indices of oxidative injury in these animals. Compared with control animals, plasma concentrations of thiobarbituric acid reactive substances (TBARS) were elevated by 62%, the concentrations of reduced sulfhydryl groups declined by 37%, and the levels of dinitrophenylhydrazine-reactive proteins (DNPH-RP) were doubled. In addition, the plasma concentrations of nitrate (NO3-) in rats exposed to glycogen plus smoke were increased three times that of control animals. Injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), immediately after smoke exposure or induction of neutropenia using either nitrogen mustard or antineutrophil antiserum, abolished the increase in concentrations of circulating NO3-, and prevented changes in plasma concentrations of TBARS, DNPH-RP, lung MPO activity, and tissue permeability index. These data suggest that neutrophil activation and the production of nitric oxide-derived oxidants contribute to the lung and plasma indices of oxidative injury in this smoke inhalation model.
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PMID:Role of neutrophils and nitric oxide in lung alveolar injury from smoke inhalation. 804 12

Studies have indicated the involvement of a glutamatergic mechanism in lithium (Li+) action. Glutamatergic agonists, such as kainic acid, are known to promote the synthesis of nitric oxide (NO) and to increase cGMP, while Li+ has displayed a similar, yet unexplained, ability to increase cGMP. NO synthesis is regarded as the principal prodromal event leading to the activation of the guanyl cyclase-cGMP transduction mechanism. In the present study, the involvement of the NO:cGMP pathway in the action of Li+ was examined, while the possibility of a glutamatergic mechanism in this response was also investigated. Parameters examined included cortical accumulation of cGMP and the stable oxidative metabolites of NO, viz. NO2- and NO3-, collectively expressed as NO2-. A significant positive correlation was observed in the in vivo cGMP and NO2- data throughout all the groups. Chronic treatment of rats with LiCl (0.3% m/m) engendered a significant increase in cGMP levels which was inhibited by the NO-synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME). Acute administration of kainic acid resulted in an increased accumulation of NO2-, also prevented by concomitant L-NAME administration. In addition, a synergistic stimulatory response on cortical NO2- was observed in the combination of LiCl and kainic acid. Collectively, these data implicate an involvement of a glutamatergic-mediated NO:cGMP transduction mechanism in the action of Li+.
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PMID:Evidence that lithium induces a glutamatergic: nitric oxide-mediated response in rat brain. 806 3

We investigated the alterations in the stable end products of nitric oxide, i.e., nitrate and nitrite, in the plasma during and after rat focal cerebral ischemia by an automated procedure based on the Griess reaction. At 2 h of middle cerebral artery (MCA) occlusion, plasma nitrate/nitrite levels were significantly higher (53 +/- 8 microM, mean +/- SD, n = 5, p < 0.05) than in rats with sham operation (36 +/- 9 microM, n = 5), and were mildly elevated at 4 h of MCA occlusion (42 +/- 9 microM, n = 5, n.s.). At 30 min of reperfusion after 2 h of MCA occlusion, plasma nitrate/nitrite levels were more markedly elevated (72 +/- 7 microM, n = 5, p < 0.01 vs. sham operation), but were moderately elevated at 2 h of reperfusion after 2 h of MCA occlusion (61 +/- 10 microM, n = 5, p < 0.05). Plasma nitrite levels were not changed during these experimental periods. Administration of 20 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) significantly decreased plasma nitrate/nitrite as well as nitrite at 30 min of reperfusion after 2 h of MCA occlusion (n = 5), but 2 mg/kg of L-NAME did not (n = 3). The effect of 20 mg/kg of L-NAME on plasma nitric oxide end products was reversed by the simultaneous administration of 200 mg/kg of L-arginine (n = 3), but not D-arginine (n = 3). The present study suggests that the L-arginine-nitric oxide pathway is activated during acute cerebral ischemia and reperfusion.
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PMID:Elevation of plasma nitric oxide end products during focal cerebral ischemia and reperfusion in the rat. 816 91

We analyzed the biological role of nitric oxide (NO) during murine Trypanosoma cruzi infection. Infection of mice with T. cruzi markedly increased NO synthesis. Administration of N-nitro-L-arginine methyl-esther (L-NAME) intraperitoneally or intragastrically diminished endogenous NO synthesis and resistance of mice to acute infection with three biologically different strains of T. cruzi. Mice protected against challenge with T. cruzi by transfer of T-cell-enriched populations from chronically infected animals, showed higher serum nitrate levels than controls non-transferred, or transferred, with T cells from non-immune mice. Administration of L-NAME abrogated transfer of resistance, suggesting NO participation in this process. Depletion of T cells from the transferred population abolished both protection and NO3- increase. On the contrary, mice chronically infected with T. cruzi showed no increased parasitemia or death upon treatment with L-NAME. The NO donor drug S-nitroso-acetyl-penicillamine was able to kill tissue culture or bloodstream trypomastigotes in vitro at biologically relevant concentrations. Conversely, NO appeared not to play a role in formation of inflammatory foci during T. cruzi infection, since infected mice treated with L-NAME showed no reduced inflammation.
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PMID:Role of nitric oxide in resistance and histopathology during experimental infection with Trypanosoma cruzi. 853 88

We tested whether NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, can prevent interleukin 2 (IL-2)-induced capillary leakage in tumour-bearing mice without compromising the therapeutic benefits of IL-2. C3H/HeJ female mice transplanted s.c. with 2.5 x 10(5) C3-L5 mammary carcinoma cells were treated with: nothing, IL-2 (ten injections of 15,000 Cetus units i.p. every 8 h), L-NAME (0.1, 0.5, or 1 mg ml-1 drinking water), IL-2 + L-NAME (0.1 or 0.5 or 1 mg ml-1 drinking water). Therapies were given in one round (IL-2, days 10-13; L-NAME, days 9-13) or in two rounds (IL-2, days 10-13 and 20-23; L-NAME, days 9-13 and days 19-23) after tumour transplantation. Capillary leakage was measured from the water contents of the pleural cavities, lungs, spleen and kidneys. Effects of the therapies on the primary tumour size and the number of spontaneous lung metastases were also recorded. NO production was measured as the nitrite + nitrate levels in the serum and in the pleural effusion. After the first round of therapies, addition of L-NAME significantly reduced IL-2-induced pulmonary oedema and water retention in the spleen in a dose-dependent manner. It also significantly reduced the IL-2-induced rise in NO levels in the serum and pleural fluid, but did not affect IL-2-induced pleural effusion or water retention in the kidney. At later stages of tumour growth (day 23), tumours themselves induced significant fluid retention in the lungs and the kidney, which was not aggravated further with the second round of IL-2 therapy. At this time, L-NAME therapy alone ameliorated tumour-induced pulmonary oedema. During both rounds of therapy different doses of L-NAME alone caused a reduction of primary tumour growth as well as spontaneous lung metastases, which improved further with the addition of IL-2. The combination therapy was at least as effective as IL-2 therapy. In summary, L-NAME had anti-tumour effects in vivo, reduced the severity of IL-2-induced capillary leakage in some organs and did not compromise anti-tumour efficacy of IL-2 therapy. Thus, L-NAME could be a valuable adjunct to IL-2-based cancer therapy.
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PMID:NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, ameliorates interleukin 2-induced capillary leakage and reduces tumour growth in adenocarcinoma-bearing mice. 854 5


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