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)

Nitric oxide (NO) was measured directly after spinal cord injury (SCI) in rats by an ESR spin-trapping technique using Fe2+ and diethyldithiocarbamate (DETC). The levels of NO and lipid peroxides expressed as thiobarbituric acid reactive substances (TBARS) were increased by SCI in the injured region and the adjacent central region. Pretreatment with 30 mg/kg of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO synthase, accelerated increases of the TBARS level and myeloperoxidase (MPO) activity in the injured tissue and caused deterioration of hind limb motor function after SCI, suggesting that NO formation by constitutive NO synthase (c-NOS) has a protective effect against cellular damage resulting from ischemia-reperfusion after SCI. Though c-NOS mRNA expression was not altered after SCI, inducible NO synthase (i-NOS) mRNA expression increased to a maximum of 24 h after SCI with progress of motor dysfunction. Intravenous injection of L-NAME (0.1 mg/kg) 6, 24, 48, and 72 h after SCI reduced the motor disturbance. These results indicate that NO induced by i-NOS may be neurotoxic in the subacute phase after SCI.
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PMID:Roles of nitric oxide in compression injury of rat spinal cord. 890 74

The purpose of the present study was to clarify the effect of topical administration of a nitric oxide synthase inhibitor on extracellular glutamate concentration in transient forebrain ischemia. Two microdialysis probes were inserted into the bilateral striata of Wistar rats. NG-Nitro-L-arginine (L-NNA) with or without L-arginine was topically administered into the unilateral striatum through one of the microdialysis probes, while Ringer's solution was perfused into the contralateral striatum as the control, and 14 minutes of forebrain ischemia was applied. The extracellular glutamate concentration during ischemia and subsequent reperfusion was statistically significantly higher on the 100 microM L-NNA-perfused side than on the control side, but 1 mM L-NNA was ineffective. When 100 microM L-NNA was perfused together with 500 microM L-arginine, the glutamate concentration did not differ from that on the control side. Moreover, administration of 500 microM L-arginine significantly suppressed the glutamate elevation after reperfusion. The fact that the lower dose of L-NNA increased the accumulation of glutamate during ischemia and reperfusion without altering blood flow may indicate that nitric oxide affords protection against ischemia neuronal damage. However, since the higher dose of L-NNA did not affect the glutamate concentration, it appears that the effect of nitric oxide on extracellular glutamate concentration in forebrain ischemia differs, depending on the degree of the inhibition of NOS activity.
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PMID:Modulation of extracellular glutamate concentration by nitric oxide synthase inhibitor in rat transient forebrain ischemia. 895 19

The contribution of nitric oxide (NO) to ischemic acute renal failure is unclear. Because polymorphonuclear neutrophils (PMN) accentuate injury in kidneys subjected to ischemia-reperfusion and because NO has potent vascular and PMN effects, we examined the contribution of NO to PMN-mediated injury in isolated perfused rat kidneys. Nonischemic and ischemic kidneys were perfused by the isolated kidney technique in the presence or absence of PMN and NO agonists [sodium nitroprusside (SNP), L-arginine (L-Arg)] or a NO synthase inhibitor [N omega-nitro-L-arginine (L-NNA)]. In nonischemic kidneys, the NOS antagonist decreased perfusion flow rate by 25% without affecting glomerular filtration rate (GFR) or tubular sodium reabsorption (TNa), whereas NOS agonist treatment had no effects. After 20 min of ischemia/60 min reperfusion in the absence of PMN NO agonist treatment potentiated ischemia-reperfusion-induced loss of GFR and TNa, whereas adding the NO antagonist lessened glomerular and tubular injury. Reperfusion of ischemic kidneys with PMN resulted in PMN retention and potentiated ischemic injury. However, increases in PMN retention as well as decreases in GFR and TNa caused by PMN were prevented by SNP and worsened by L-NNA. Moreover, in nonischemic kidneys, activated PMN caused renal injury and PMN retention, which were prevented by SNP and worsened by L-NNA. In conclusion, 1) NO worsens ischemic injury in the absence of PMN, and 2) NO prevents the PMN component of ischemic renal injury by blocking PMN retention and the deleterious effects of activated PMN on glomerular and tubular function.
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PMID:Nitric oxide prevents neutrophil-mediated acute renal failure. 903 48

The stimulation of NMDA receptor activates NO dependent cGMP biosynthesis with dynamic and extent different for hippocampus and brain cortex. The significantly higher NO mediated cGMP level was observed in hippocampus than in brain cortex. NMDA receptor stimulation increases NO mediated cGMP formation about 8 fold in hippocampus and 2.5 fold in brain cortex as compared to basal value (2 mM CaCl2). The activity of NO synthase and the basal level of cGMP in unstimulated slices were only slightly higher in hippocampus then in brain cortex. The CA2+ calmodulin dependent NO synthase was found in brain membrane and cytosol fraction. The enzyme activity was not affected by glucocorticoids, even after 20 days of hydrocortisone treatment in a dose of 40 mg/kg b.w. Brain ischemia induced by ligation of both common carotid arteries in gerbils increases significantly NOS activities as well as the level of cGMP and putrescine but decreases mono-ADP-ribosylation of brain proteins during reperfusion period. The ischemia evoked changes of NOS/cGMP were eliminated by specific inhibitor of neuronal form of NOS, 7-Nitrodazole (7NI) administered in a dose of 25 mg/kg b.w. 5 min. before ischemia. This inhibitor has no effect on the level of putrescine enhanced during ischemia and also biphasically during reperfusion. The inhibitor of guanylate cyclase, LY 83583 administered in a dose of 6 mg/kg b.w. 5 min before ischemia diminishes not only the enhanced level of cGMP but also NOS activity stimulated by ischemia. These results indicate that activation of NMDA receptor stimulates more significantly NO/cGMP production in hippocampus than in brain cortex suggesting the role of NO in neuronal form of NOS and inhibitor of guanylate cyclase protect the brain against excessive production of nitric oxide and cGMP during ischemia-reperfusion. These compounds may offer a new strategy in the therapy of brain ischemia.
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PMID:NMDA receptor mediated nitric oxide dependent cGMP synthesis in brain cortex and hippocampus. Effect of ischemia on NO related biochemical processes during reperfusion. 910 Feb 45

Although it is well known that brain ischemia is dominantly caused by hypoxia and hypoglycemia, it is still unclear how hypoxia participates in ischemia. We studied the changes in neuronal nitric oxide synthase (nNOS) and the effect of the NOS inhibitor NG-nitro-L-arginine (NNA) on hypoxia. In vivo hypoxia (5% O2/95% N2 for 30 min) induced mild degenerative neuronal changes (shrunken and eosinophilic somata with picnotic nuclei) in neurons of the CA3, the hilus of the dentate gyrus (DG) and the DG, but not in the CA1. At 3 and 7 days after hypoxia, levels of nNOS protein were significantly enhanced to 153 and 209%, but iNOS protein could not be detected. The numbers of nNOS-immunopositive neurons were significantly enhanced to 145 and 191% in the CA3, 145 and 178% in the hilus of the DG, and 243 and 387% in the DG after 3 and 7 days, respectively. In contrast, no statistical difference was determined in the CA1. We further examined the effect of NNA administered at 5 min and 3, 6, and 24 h after hypoxia. Administration of NNA (0.1 and 1 mg/kg, i.p.) significantly decreased the number of damaged neurons in the hilus of the DG and the DG. However, higher doses of NNA (10 mg/kg, i.p.) did not prevent damage. These results suggest that hypoxia alone induces enhancement of nNOS protein and nNOS immunoreactivity in neurons of the hippocampus and that NNA has biphasic effects against hypoxia-induced neuronal damage in the hilus of the DG and the DG.
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PMID:In vivo hypoxia-induced neuronal damage with an enhancement of neuronal nitric oxide synthase immunoreactivity in hippocampus. 922 38

Inhibition of nitric oxide (NO) synthesis in mesenteric microvessels increases leukocyte rolling. The objective of this study was to determine whether inducible NO synthase (iNOS) can modulate tumor necrosis factor-alpha (TNF-alpha)-induced leukocyte rolling. Leukocyte rolling was examined using intravital microscopy of TNF-alpha-treated feline mesenteric microvasculature. Leukocyte rolling increased progressively over 3 h of TNF-alpha treatment. Pretreatment with the selective iNOS inhibitor aminoguanidine further doubled TNF-alpha-induced leukocyte rolling. Aminoguanidine alone did not affect baseline blood pressure or leukocyte kinetics. However, in the same animals NG-nitro-L-arginine methyl ester caused a rapid increase in blood pressure, confirming that constitutive NOS activity persisted in aminoguanidine-treated animals. Furthermore, aminoguanidine did not affect leukocyte rolling in an acute model of leukocyte recruitment (ischemia/reperfusion), suggesting that the exacerbated rolling induced by aminoguanidine with TNF-alpha as a stimulus was not a nonspecific effect. Addition of the NO donor spermine-NO had no effect on TNF-alpha-associated leukocyte rolling. These data raise the possibility of a physiological role for the increased production of NO from iNOS, i.e., regulation of leukocyte rolling and potentially the inflammatory response.
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PMID:Endogenous but not exogenous nitric oxide decreases TNF-alpha-induced leukocyte rolling. 931 65

Ischemia-reperfusion (IR) lung injury occurs after various clinical procedures, including cardiopulmonary bypass. It is not clear whether endogenous nitric oxide (NO) is protective or injurious in lungs subjected to IR. Thus, in this study we examined the contribution of endogenous NO to IR injury in isolated, blood-perfused rat lungs. Lungs of male Wistar rats (300 g) were subjected to 30 min ischemia and 180 min reperfusion (I30R180). Lungs were sampled for inducible nitric oxide synthase (i-NOS) mRNA expression (each n = 3) and NOS enzyme activity (each n = 4) at different time points. NOS inhibitors NG-nitro-L-arginine-methyl ester (10[-4] M) and aminoguanidine (10[-4] M) were used to study the contribution of NO to IR injury in lungs subjected to I30R30 and I30R180. The contribution of i-NOS to IR lung injury was studied by inducing i-NOS enzyme with Salmonella lipopolysaccharide, followed by I30R30. We found that ischemia-reperfusion alone can upregulate i-NOS mRNA and i-NOS enzyme activity (p < 0.05, ANOVA), but downregulate constitutive NOS enzyme activity over 180 min reperfusion. Endogenously produced NO is protective against lung injury in I30R180 in normal rats and lung injury in I30R30 in septic rats. NO is also pivotal in maintaining pulmonary vascular homeostasis in septic rat lungs undergoing IR.
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PMID:The role of endogenous nitric oxide in modulating ischemia-reperfusion injury in the isolated, blood-perfused rat lung. 944 9

Changes in the regional distribution of protein kinase C (PKC) after transient focal cerebral ischemia in SV-129 mice were assessed by quantitative autoradiography using [3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding. [3H]PDBu binding did not change up to 10 min after reperfusion of 3 h ischemia, but at 1 h after reperfusion markedly decreased to 40-50% of control (pre-ischemia) in the ipsilateral striatum and the middle cerebral artery (MCA) region of cortex in SV-129 mice. The binding decreased to 20% of control at 3-7 days after reperfusion, but did not change in the ipsilateral anterior cerebral artery (ACA) territory or the contralateral brain. In the ipsilateral substantia nigra, which lies outside the ischemic zone, [3H]PDBu binding was not significantly changed compared to the control values (pre-ischemia) at early phase (up to 3 h after reperfusion), but marked reduction of the binding was observed 1 day after reperfusion. After 3 h ischemia followed by 3 h reperfusion, the morphological damage and the decrease in [3H]PDBu binding in the ipsilateral striatum and the MCA region of cortex was smaller in mice lacking the expression of neuronal nitric oxide synthase (type I NOS) gene mutant mice compared to wild-type (SV-129 and C57black/6) mice. Our data suggest that postischemic alterations of PKC binding activity were observed in the ischemic and non-ischemic lesions in the mouse brain.
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PMID:Alteration of protein kinase C activity after transient focal cerebral ischemia in mice using in vitro [3H]phorbol-12,13-dibutyrate binding autoradiography. 945 94

We have already reported that the concentration of nitric oxide (NO) increases during and after cerebral ischemia and a selective inhibitor of neuronal NO synthase (nNOS) suppresses this increase and subsequently mitigates brain damage in rats. Although the selective inhibition of nNOS is a promising pharmacological strategy for the treatment of stroke, the role of inducible NOS (iNOS) remains to be clarified. Toward this end, we investigated temporal alterations in iNOS mRNA by the RT-PCR method in a rat model of middle cerebral artery (MCA) occlusion. We found that iNOS mRNA in the ischemic hemisphere began to increase at 3 hr and reached the maximum level at 24 hr of reperfusion following 3 hr of MCA occlusion. However, quantitative analysis revealed that no significant difference existed between 6 hr or 24 hr reperfusion group and their respective time-matched sham operation group. In addition, neither Western blotting nor immunocytochemical study disclosed an apparent induction of iNOS at any time points examined. Similar results were obtained at 24 hr of permanent MCA occlusion. Taken together, these data indicate that iNOS induction during and after MCA occlusion may be not a critical event for the development of infarction caused by ischemia itself.
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PMID:[Lack of evidence that inducible nitric oxide synthase participates in the development of ischemic brain damage]. 955 72

Electron microscopy immunocytochemical study was performed to clarify ultrastructural localization and role of endothelial nitric oxide synthase (EC-NOS) in the endothelial cells (EC) of rat hippocampal vessels after transient cerebral ischemia. EC-NOS immunoreactivity was found in the endothelial cells in association with plasma membrane, sub-plasmalemmal vesicles, basal membrane and in cytosol (cytoplasm free of subcellular organelles). A sharp transient increase in immunoreactivity of NOS was observed at 10 min up to 1 hour after ischemia. The results of the present study indicate that NO, as a potent vasodilator, may play a protective role in ischemic brain damage.
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PMID:Endothelial nitric oxide synthase in vascular endothelium of rat hippocampus after ischemia: evidence and significance. 959 52


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