Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.5.1.19 (NOS)
7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological evidence supports a role of a transient decreased endogenous nitric oxide (NO) synthesis in ovalbumin (OVA)-induced early airway hyperresponsiveness in guinea pigs. However, no data are available regarding the expression and activity of the constitutive NO synthases (cNOS; NOS1 and NOS3, nNOS and eNOS, respectively) in this model. Therefore, we evaluated cNOS activity (conversion of L-[3H]arginine to L-[3H]citrulline in the presence of Ca2+ and calmodulin), nitrate and nitrite (NOx) concentration (modified Griess method), and NOS1 and NOS3 protein expression (Western blot) in lung homogenates and in the tracheal smooth muscle from OVA-immunized and multiple aerosol-challenged guinea pigs (six challenges, once daily). The expression and activity of the inducible NOS isoform (NOS2), the levels of exhaled NO, and the in vivo airway reactivity were also determined. Constitutive NOS activity and NO(x) concentration were significantly lower 6 h after the last OVA challenge as compared with saline exposure, being similar at 24 h. Expression of NOS1 paralleled cNOS activity, which was reduced 6, but not 24 h after OVA challenge. The decrease in NOS1 expression was accompanied by a significant decrease in the amounts of exhaled NO and by a maximal airway hyperresponsiveness to histamine. The levels of NOS3 were not modified at the two time points evaluated, and no NOS2 expression and activity were found at any time point. Similar modifications were observed in the tracheal smooth muscle. We conclude that OVA stimulation in immunized guinea pigs induced a transient reduction in NOS1 protein expression and activity in the respiratory system, which probably participates in airway hyperresponsiveness.
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PMID:Decreased pulmonary and tracheal smooth muscle expression and activity of type 1 nitric oxide synthase (nNOS) after ovalbumin immunization and multiple aerosol challenge in guinea pigs. 1143 53

The regional distribution of catalytic NOS activity was studied in the lumbosacral segments of the spinal cord of the rabbit during single (8-min), twice (8-, 8-min) and thrice repeated (8-, 8-, 9-min) sublethal ischemia followed each time by 1 h of reperfusion. Single ischemia/reperfusion induced a significant increase of cNOS activity in almost all spinal cord regions, with the exception of non-significant increase in the dorsal horn. Sublethal ischemia repeated twice produced a significant decrease of enzyme activity in the intermediate zone and ventral horn and an increase in the white matter columns. Within thrice repeated ischemia, the activity of cNOS in the gray matter regions was similar to that found after a single ischemia/reperfusion. For all the animals subjected to single and twice repeated sublethal ischemic insults, there was no neurological impairment. Following thrice repeated ischemic insults, four out of five of the experimental animals recovered only partially and one was completely paraplegic. Our results do not indicate a cumulative effect of repeated sublethal ischemia on cNOS activity and, consequently, on NO production. The NO generated during thrice repeated ischemia/reperfusion appears to have a detrimental effect on the neurological outcome.
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PMID:The regional changes of the catalytic NOS activity in the spinal cord of the rabbit after repeated sublethal ischemia. 1156 16

1. We have shown that exogenously administered L-arginine protects against water immersion restraint (WIR) stress-induced gastric mucosal lesions in rats through preservation of nitric oxide (NO) generation via constitutive nitric oxide synthase (cNOS), but not inducible nitric oxide synthase (iNOS), in the gastric mucosa. We have also indicated that impaired gastric mucus synthesis and secretion occur through a decrease in gastric cNOS activity in WIR-stressed rats. Therefore, in the presesnt study, we examined whether exogenously administered L-arginine exerts a protective effect against WIR stress-induced gastric mucosal lesions in rats through preservation of gastric mucus synthesis and secretion by NO generated from the administered amino acid via cNOS in the gastric mucosa. 2. Rats were subjected to WIR stress for 3 and 6 h. Either L-arginine (150-600 mg/kg) or D-arginine (600 mg/kg) was injected intraperitoneally 0.5 h prior to WIR stress. Either N(G)-monomethyl L-arginine (L-NMMA; 100 mg/kg) or N(G)-monomethyl D-arginine (D-NMMA; 100 mg/kg) was injected subcutaneously 0.5 h prior to WIR stress. Total NOS, cNOS, iNOS, nitrite and nitrate (breakdown products of NO), hexosamine (an index of gastric mucin) and adherent mucus were assayed in the gastric mucosa. 3. Pretreatment with L-arginine, but not D-arginine, protected against gastric mucosal lesions in rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Pretreatment with L-arginine, but not D-arginine, attenuated decreases in hexosamine and adherent mucus concentrations and cNOS activity and increases in total NOS and iNOS activities and nitrite/nitrate concentration in the gastric mucosal tissue of rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Both the protective effect of L-arginine against gastric mucosal lesions and the attenuating effect of the amino acid on the decreases in gastric mucosal hexosamine and adherent mucus concentrations and cNOS activity in rats subjected to WIR stress for 6 h were counteracted by cotreatment with L-NMMA, a nitric oxide synthase inhibitor, but not D-NMMA. 4. These results suggest that exogenously administered L-arginine exerts a protective effect against stress-induced gastric mucosal lesions in rats at least partly through preservation of gastric mucus synthesis and secretion by NO produced from the administered amino acid via cNOS in gastric mucosal tissue.
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PMID:L-arginine protects against stress-induced gastric mucosal lesions by preserving gastric mucus. 1190 59

This study examined the expression of constitutive endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) in the sciatic nerve of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis showed that both eNOS and iNOS expressions in the sciatic nerves of rats increased significantly during the peak stage of EAN, but declined thereafter. Only minimal amounts of these enzymes were identified in normal rat sciatic nerves. Immunohistochemical studies showed that eNOS was increased in vascular endothelial cells and Schwann cells, but not in inflammatory cells, during the peak stage of EAN. However, iNOS was found mainly in inflammatory macrophages in sciatic nerve EAN lesions.These findings suggest that, depending on the stage of peripheral nervous system autoimmune disease, the increased expressions of both eNOS and iNOS might be involved in either the production of detrimental effects during the induction stage of EAN or in the recovery from EAN paralysis.
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PMID:Expression of constitutive endothelial and inducible nitric oxide synthase in the sciatic nerve of Lewis rats with experimental autoimmune neuritis. 1202 Sep 59

1. A deficiency of constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO), due to reduced availability of L-arginine, importantly contributes to allergen-induced airway hyperresponsiveness (AHR) after the early asthmatic reaction (EAR). Since cNOS and arginase use L-arginine as a common substrate, we hypothesized that increased arginase activity is involved in the allergen-induced NO deficiency and AHR. 2. Using a guinea-pig model of allergic asthma, we addressed this hypothesis by examining the effects of the specific arginase inhibitor N(omega)-hydroxy-nor-L-arginine (nor-NOHA) on the responsiveness to methacholine of isolated perfused tracheae from unchallenged control animals and from animals 6 h after ovalbumin challenge. Arginase activity in these preparations was investigated by measuring the conversion of L-[14C]arginine to [14C]urea. 3. Airways from allergen-challenged animals showed a 2 fold (P<0.001) increase in responsiveness to intraluminal (IL) administration of methacholine compared to controls. A similar hyperresponsiveness (1.8 fold, P<0.01) was observed in control airways incubated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM, IL), while L-NAME had no further effect on the airways from challenged animals. 4. Remarkably, 5 microM nor-NOHA (IL) normalized the hyperresponsiveness of challenged airways to basal control (P<0.001), and this effect was fully reversed again by 0.1 mM L-NAME (P<0.05). Moreover, arginase activity in homogenates of the hyperresponsive airways was 3.5 fold (P<0.001) enhanced compared to controls. 5. The results indicate that enhanced arginase activity contributes to allergen-induced deficiency of cNOS-derived NO and AHR after the EAR, presumably by competition with cNOS for the common substrate, L-arginine. This is the first demonstration that arginase is involved in the pathophysiology of asthma.
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PMID:Increased arginase activity underlies allergen-induced deficiency of cNOS-derived nitric oxide and airway hyperresponsiveness. 1202 42

The role of islet constitutive nitric oxide synthase (cNOS) in insulin-releasing mechanisms is controversial. By measuring enzyme activities and protein expression of NOS isoforms [i.e., cNOS and inducible NOS (iNOS)] in islets of Langerhans cells in relation to insulin secretion, we show that glucose dose-dependently stimulates islet activities of both cNOS and iNOS, that cNOS-derived nitric oxide (NO) strongly inhibits glucose-stimulated insulin release, and that short-term hyperglycemia in mice induces islet iNOS activity. Moreover, addition of NO gas or an NO donor inhibited glucose-stimulated insulin release, and different NOS inhibitors effected a potentiation. These effects were evident also in K+-depolarized islets in the presence of the ATP-sensitive K+ channel opener diazoxide. Furthermore, our results emphasize the necessity of measuring islet NOS activity when using NOS inhibitors, because certain concentrations of certain NOS inhibitors might unexpectedly stimulate islet NO production. This is shown by the observation that 0.5 mmol/l of the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) stimulated cNOS activity in parallel with an inhibition of the first phase of glucose-stimulated insulin release in perifused rats islets, whereas 5.0 mmol/l of L-NMMA markedly suppressed cNOS activity concomitant with a great potentiation of the insulin secretory response. The data strongly suggest, but do not definitely prove, that glucose indeed has the ability to stimulate both cNOS and iNOS in the islets and that NO might serve as a negative feedback inhibitor of glucose-stimulated insulin release. The results also suggest that hyperglycemia-evoked islet NOS activity might be one of multiple factors involved in the impairment of glucose-stimulated insulin release in type II diabetes mellitus.
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PMID:Role of nitric oxide synthase isoforms in glucose-stimulated insulin release. 1205 99

Nitric oxide (NO) plays important roles in the regulation of cerebral blood flow (CBF) in the perinatal period. The present study was undertaken to investigate the influence of intrauterine ischemia-hypoxia (IH) on the expression of endothelial NO synthase (eNOS) in fetal brains in rats. To induce intrauterine IH insult, bilateral uterine arteries were ligated on day 17 of pregnancy. Activities and mRNA levels in the brain of the fetuses were examined on days 17-21 of pregnancy. The IH insult caused the increase in both activities and mRNA levels of eNOS on day 21 of pregnancy, whereas there were no significant changes in neuronal NOS mRNA levels. Endothelial NOS expression in the fetal brains was increased by intrauterine IH insult, suggesting that eNOS may contribute to the maintenance of CBF against ischemia or hypoxia conditions in the fetal rats.
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PMID:Effect of intrauterine ischemia-hypoxia on endothelial nitric oxide synthase in fetal brain in rats. 1216 34

In patients with cyclosporine-induced hypertension, upregulation of the nitric oxide system and oxidative stress were shown, which could induce hypertension, remodeling, and chronic rejection by increasing nitric oxide catabolism. However, it is still debated whether cyclosporine and tacrolimus exert a different action. The aim of the current study was to compare the effects of cyclosporine and tacrolimus on markers of oxidative stress and endothelial dysfunction in kidney transplant patients with posttransplant hypertension. Monocyte p22, a NADH/NADPH system subunit, transforming growth factor-beta (TGF-beta), heme oxygenase-1 (HO-1), and endothelial NOS gene expression were measured in 16 patients. Angiotensin II is a potent stimulator of oxidative stress and angiotensin-converting enzyme inhibition may blunt this effect. Therefore, the same parameters were measured before and after 2 months of treatment with ramipril (5 mg/d). At baseline, in cyclosporine-and tacrolimus-treated patients, p22 and TGF-beta mRNA were similarly increased in comparison with normotensive healthy controls (0.90 +/- 0.05 d.u. and 0.83 +/- 0.05 in cyclosporine, 0.89 +/- 0.07 and 0.84 +/- 0.05 in tacrolimus; 0.53 +/- 0.07 and 0.75 +/- 0.03 in controls, respectively; p < 0.001). Endothelial NOS mRNA was increased in cyclosporine-and tacrolimus-treated patients in comparison with controls (0.92 +/- 0.09, 0.96 +/- 0.04, and 0.37 +/- 0.05 respectively; p < 0.001), whereas no difference was found between patients and controls in HO-1 mRNA. Ramipril reduced blood pressure (from 140 +/- 11/91 +/- 7 mm Hg to 129 +/- 6/85 +/- 5 mm Hg in cyclosporine and from 138 +/- 7/92 +/- 7 mm Hg to 127 +/- 10/82 +/- 6 mm Hg in tacrolimus group; p < 0.02 with no difference between groups). Ramipril also reduced p22 (to 0.83 +/- 0.05 in cyclosporine, p < 0.03 and to 0.81 +/- 0.08 in tacrolimus; p < 0.01) and TGF-beta mRNA (to 0.72 +/- 01 in cyclosporine, p < 0.02, and to 0.73 +/- 0.05 in tacrolimus; p < 0.01) with no difference between groups, but it did not change HO-1 and ecNOS mRNA. Cyclosporine and tacrolimus induce a comparable oxidative stress in kidney transplant patients with posttransplant hypertension. The association of ramipril normalizes blood pressure and reduces the oxidative stress induced by both drugs.
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PMID:Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. 1235 26

We have previously demonstrated that exposure of human macrophages to morphine results in transient inhibition of cell migratory behavior and adoption of an inactive conformation followed by a return from inhibition resulting in a significant increase in migration velocity and number of activated cells. In the current report, we demonstrate that the return to activation is nitric oxide dependent and inhibited by prior exposure to the opiate antagonist, naloxone. Exposure of macrophages to morphine for 6 hours resulted in a marked inhibition of cell activity and shift of the cell confirmation from amoeboid to round. The inactivation period lasted approximately 2 hrs and was followed by a period of hyperactivity. Incubation of macrophages with naloxone, prior to addition of morphine, inhibited both inactivation and hyper activation phases whereas, naloxone administration just prior to the hyper activation phase did not affect subsequent hyper activation. Morphine acutely stimulates the transient release of nitric oxide (NO) resulting in subsequent macrophage rounding and inactivation. Prolonged observation of the cells revealed another phase of NO release 12 hours following initial morphine exposure that was characterized by prolonged NO production. These data are consistent with acute constitutive NO synthase activation and inducible NO synthase activation following prolonged morphine exposure. Release of NO and changes in cellular activation mediated by morphine was abrogated by NOS, or morphine inhibitors, added prior to morphine exposure. In contrast, NOS, or morphine inhibitors, added during the inhibitory phase had no impact on the subsequent hyper activation phase. It did, however, have an impact on the hyper activation phase when added prior to morphine. These data demonstrate that morphine is capable of induction of both cNOS and iNOS coupled NO release that regulates the macrophage activation state. This may provide insight into the functioning of morphine following periods of trauma or stress when the levels of the opiate increase and, subsequently, inflammatory function is markedly altered.
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PMID:Morphine stimulates iNOS expression via a rebound from inhibition in human macrophages: nitric oxide involvement. 1260 12

Isolated using Langendorff technique hearts of male Wistar rats were ischemized for 30 min and reperfused for 40 min. Both iNOS expression determined by immunoblotting, and its activity shown by a modified Griess method have been found to predominate in the right ventricle over the left one, as compared to cNOS activity which prevailed in the left ventricle. The latter significantly diminished after an ischemic injury in the left ventricle. On the contrary, an expression of iNOS and the total NOS activities increased progressively after ischemia and postischemic reperfusion; all the values in the right ventricle were higher than in the left one. The high level of iNOS expression in the right ventricle in a postischemic period decreased during reperfusion, although an activity of the enzyme went on elevating. These data can give an evidence for different regulation of NO synthesis in right or left ventricles of the heart, including normal conditions or ischemia.
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PMID:[Expression of iNOS and activities of iNOS and cNOS in right and left ventricles of the isolated heart during ischemia and reperfusion]. 1266 15


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