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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although nitric oxide (NO) has been shown to play an important role in the pathophysiology of cerebral ischemia, its contribution to the pathogenesis of experimentally induced thromboembolic stroke is unknown. In this study, we pharmacologically manipulated NO levels in the acute post-thrombotic stage and determined the effects on behavior and histopathology. The following drugs were used: nitro-L-arginine-methyl ester (L-NAME), a non-specific endothelial and neuronal nitric oxide synthase (eNOS and nNOS) inhibitor, 3-bromo-7-nitroindazole (7-NI), a specific inhibitor for nNOS, the NO precursor, exogenous L-arginine and the NO-donor, 3-morpholino-sydnonimine (SIN-1). Male Wistar rats (n = 76) were randomly assigned to receive vehicle or drug immediately after common carotid artery thrombosis (CCAT). Regional measurements of cortical NOS activity using the [3H]L-arginine to [3H]L-citrulline conversion assay were decreased 1 h after treatment with L-NAME and 7-NI by 50 and 65%, respectively; hippocampal NOS activity was reduced with L-NAME by 35% and with 7-NI by 65%. L-NAME significantly worsened forelimb placing as compared to other groups. 7-NI accelerated sensorimotor recovery. Water maze retention deficits were noted 48 h after CCAT and these were exacerbated by L-NAME treatment. Histopathological protection was conferred in the hippocampus by 7-NI and SIN-1; conversely, L-NAME increased neuronal injury in the contralateral cortex. L-arginine had no effect on these outcomes. In conclusion, both structural and functional consequences of CCAT can be aggravated by limiting endothelial NO production in the acutely post-thrombotic brain. In contrast, inhibition of nNOS and infusion of an NO donor has a beneficial effect on pathology.
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PMID:The role of nitric oxide in the pathophysiology of thromboembolic stroke in the rat. 921 60

The effect of N omega-nitro-L-arginine methyl ester (L-NAME) on ischemic neuronal damage was studied in a rat model of permanent focal cerebral ischemia in terms of ipsilateral and contralateral cortical and cerebellar tissue lipid peroxides. Forty-five male Swiss Albino rats were assigned to one of four groups; sham operated as control, subjected to right middle cerebral artery occlusion or injection of L-NAME (10 mg/kg i.p.) either 30 min before or just after right middle cerebral artery occlusion. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde and conjugated diene per milligram of protein. Malondialdehyde values following 60 min of ischemia relative to contralateral cortex and conjugated diene levels in 0, 10 and 60 min of ischemia were found to be higher in ipsilateral cortex than in contralateral cortex. On the other hand, contralateral cerebellar malondialdehyde levels after 0 and 60 min of ischemia and conjugated diene levels after 0, 10 and 60 min of ischemia were higher than those in ipsilateral cerebellum. Pharmacological inhibition of nitric oxide synthase by L-NAME before or just after permanent middle cerebral artery occlusion significantly decreased the malondialdehyde and conjugated diene levels in both the cortex and the cerebellum. No significant differences were found in malondialdehyde values between rats that had been pre- and post-treated with L-NAME, but conjugated diene levels in the post-treated group seemed to be significantly lower than those in the pretreated group. On the whole, these results suggest that malondialdehyde and conjugated diene represent early biochemical markers of lipid peroxidation in ischemic tissues, reflecting the radical-mediated tissue damage.
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PMID:Inhibitory role of N omega-nitro-L-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, on brain malondialdehyde and conjugated diene levels during focal cerebral ischemia in rats. 946 54

To date, the role of nitric oxide (NO) in mediation of cerebrovascular regulation during spreading depression (SD) in rats remains controversial. Studies are compromised by indirect assay of 'regional' nitric oxide synthase activity (NOS) and/or inappropriate doses of antagonists. The present study utilises direct electrochemical detection in the pia to demonstrate a local, biphasic release of NO associated with each wave of cortical depolarisation. The mean peak of SD-induced NO release was 0.35 microM, which was significantly inhibited by L-N(G)-nitroarginine methyl ester (L-NAME) pre-treatment. Changes in cerebrovascular flux remained intact following treatment with L-NAME, indicating little role for NO in mediation of rat SD blood-flux changes. Mean peak NO release was found to be lower than that observed in rat cerebral ischaemia studies (approximately 4 microM) and in SD in the cat gyrencephalic brain (approximately 0.8 microM).
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PMID:Nitric oxide does not mediate cerebral blood flow changes during cortical spreading depression in the anaesthetised rat. 969 32

The interaction between nitric oxide (NO.) and focal cerebral ischemia is multifaceted. Experiments have shown that inhibition of nitric oxide synthase (NOS) either ameliorates or exacerbates focal cerebral ischemia. Recent in vitro experiments have shown that NOS activity is pH-dependent. Previous work from this laboratory has demonstrated that N(G)-nitro-L-arginine-methyl-ester (L-NAME) mitigated cerebral ischemia independent from regional cerebral blood flow (rCBF) changes during moderate focal cerebral ischemia. This study examined the effects of L-NAME inhibition on brain pH(i), rCBF, and NADH redox state during 3 h of severe focal cerebral ischemia. Fifteen fasted rabbits under 1.5% halothane were equally divided into three groups: ischemic controls and two drug groups receiving either 1.0 or 10 mg/kg L-NAME intravenously 30 min prior to ischemia. In the ischemic controls, brain pH(i) declined from 6.95+/-0.04 to 6.60+/-0.05, rCBF declined from 48+/-7 to 10+/-3 ml/100 g/min, and NADH fluorescence increased by 149+/-15% 3 h after onset of ischemia (p<0.01 for all three parameters). L-NAME at either dose did not significantly alter these values. Infarct volume was not significantly different between both the L-NAME treated groups and the ischemic control group. This data suggests that during severe focal cerebral ischemia, NO. mechanisms of injury have a less important punitive role. One possible explanation is that the severity of acidosis secondary to anaerobic metabolism during severe focal cerebral ischemia attenuates NOS activity.
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PMID:Is intracellular brain pH a dependent factor in NOS inhibition during focal cerebral ischemia? 1067 29

The purposes of this study were to investigate the role of nitric oxide (NO), nitric oxide synthase (NOS), and 70 kDa heat shock protein in brain ischemic tolerance induced by ischemic preconditioning and lipopolysaccharide. Focal cerebral ischemia was induced in rats by intraluminal middle cerebral artery occlusion. Infarct volume was significantly reduced (1) in rats subjected to 3 min ischemia 72 h prior to 60 min ischemia; (2) in rats administered lipopolysaccharide (0.5 mg/kg; i.p.) 72 h prior to 60 min ischemia compared with controls. The beneficial effect of ischemic preconditioning was unchanged despite prior administration of nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Conversely, the protective effect of lipopolysaccharide was nullified by L-NAME. Using immunohistochemical techniques, we observed that (1) ischemic preconditioning but not lipopolysaccharide induces the expression of 70 kDa heat shock protein in cerebral cortex and (2) lipopolysaccharide induces early increased expression of endothelial NOS in cerebral blood vessels. The results suggest that (1) endothelium-derived NO plays a role of a trigger in the brain tolerance induced by lipopolysaccharide, and (2) 70 kDa heat shock protein is involved in the protection afforded by ischemic preconditioning but not by lipopolysaccharide.
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PMID:Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance. 1068 98

The role of oxygen free radical generation during reversible focal cerebral ischemia and its relationship to nitric oxide mediated mechanisms were examined. In this study, a left frontal cortex microdialysis probe was placed into the previously defined ischemic penumbra region and perfused with a salicylate/CSF solution in the presence or absence of the nitric oxide synthase (NOS) inhibitor L-NAME. Rats were then subjected to transient left hemisphere focal cerebral ischemia. Dialysate was collected at baseline and during the ischemic/reperfusion phase, and the hydroxylation products of salicylate were measured by HPLC with electrochemical detection. A significant elevation of free radical adduct formation was observed in the penumbra region during ischemia/reperfusion. This elevation was significantly attenuated by L-NAME during the reperfusion phase. Elevation of free radical adduct formation within the penumbra region during cerebral ischemia/reperfusion may be mediated in part by NOS-dependent mechanisms.
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PMID:Attenuation of free radical generation during reversible focal cerebral ischemia with the nitric oxide inhibitor, L-NAME (L-N(G)-nitro-L-arginine methyl ester). 1079 96

A beneficial role of nitric oxide (NO) after cerebral ischemia has been previously attributed to its vascular effects. Recent data indicate a regulatory role for NO in initial leukocyte-endothelial interactions in the cerebral microcirculation under basal and ischemic conditions. In this study, the authors tested the hypothesis that endogenous NO production during and/or after transient focal cerebral ischemia can also be neuroprotective by limiting the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left middle cerebral artery and the left common carotid artery. The effect of NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, intraperitoneally), an NO synthase inhibitor, was examined at 48 hours after ischemia on both infarct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical infarct volume by 34% and increased cortical myeloperoxidase activity by 60%, whereas administration of L-NAME at 1, 7, and 22 hours of reperfusion had no effect. Such exacerbations of infarction and myeloperoxidase activity produced when L-NAME was given 5 minutes after the onset of ischemia were not observed in rats rendered neutropenic by vinblastine. These results suggest that after transient focal ischemia, early NO production exerts a neuroprotective effect by modulating neutrophil infiltration.
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PMID:Modulation by nitric oxide of cerebral neutrophil accumulation after transient focal ischemia in rats. 1082 31

Neurons that express neuronal nitric oxide synthase (nNOS) are selectively spared from nitric oxide (NO)-induced cytotoxicity in acute cerebral ischemia and neurodegenerative conditions but the mechanism of this resistance is unknown. To identify specific gene products which may mediate this resistance, we performed polymerase chain reaction (PCR)-based subtractive hybridization on a mouse macrophage cell line treated with either L-NG-nitroarginine methyl ester (L-NAME, 1 mM, 1 h), an inhibitor of NOS, or with diethylamine NONOate (DEA NONO, 200 microM, 1 h), an NO donor. NO-treated cultures showed an acute induction of mRNA (less than 1 h after treatment) and protein (15 min) for the mitochondrial enzyme cytochrome c oxidase (CcO) as shown by Northern or Western blot analysis, respectively. Cytochrome c oxidase activity assay showed constant activity in NO-treated cultures, as compared to L-NAME-treated cultures. NO directly inhibits CcO, the terminal electron acceptor in mitochondrial oxidative respiration. Up-regulation of this enzyme by NO, therefore, appears to maintain vital CcO activity and cellular energy stores, thus contributing to selective sparing of nNOS neurons.
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PMID:Nitric oxide mediated induction of cytochrome c oxidase mRNA and protein in a mouse macrophage cell line. 1087 72

Protective effects of NOS inhibitors and free radical scavengers in cerebral ischemia are well documented. The present study was undertaken to determine the possible effects of NOS inhibition on brain antioxidants. Levels of both enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)] and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME), D-NAME or 7-nitroindazole (7-NI) have been investigated. NOS activity and antioxidant levels in the rat cerebellum and medulla were estimated 1 h after treatment with L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg, i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME also exhibited significant NOS inhibition. The activity of SOD and the GSH level remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100 mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L-NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not affect catalase activity in the rat brain. Thus, NOS inhibition by the three agents did not have major effects on brain antioxidant levels.
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PMID:Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a preliminary report. 1093 75

A perfusion model of global cerebral ischemia was used for the immunohistochemical study of changes in the glutamate-nitric oxide (NO) system in the rat cerebellum and cerebellar nuclei during a 0-14 h reperfusion period after 30 min of oxygen and glucose deprivation, with and without administration of 1.5 mM N(omega)-nitro-L-arginine methyl ester (L-NAME). While immunostaining for N-methyl-D-aspartate receptor subunit 1 (NMDAR1) showed no marked changes during the reperfusion period, neuronal NO synthase (nNOS) immunostaining increased in stellate and basket cells, granule cells and neurons of the cerebellar nuclei. However, global cerebellar nNOS concentrations determined by Western blotting remained largely unchanged in comparison with actin expression. Inducible NOS (iNOS) immunostaining appeared in Purkinje cells and neurons of the cerebellar nuclei after 2-4 h of reperfusion and intensified during the 6-14 h period. This was reflected by an increase in global cerebellar iNOS expression determined by Western blotting. Immunostaining for protein nitrotyrosine was seen in Purkinje cells, stellate and basket cells, neurons of the cerebellar nuclei and glial cells in controls, and showed a progressive translocation in Purkinje cells and neurons of the cerebellar nuclei from an initial perinuclear or nuclear location towards the periphery. At the end of the reperfusion period the Purkinje cell apical dendrites were notably retracted and tortuous. Prior and concurrent L-NAME administration eliminated nitrotyrosine immunostaining in controls and blocked or reduced most of the postischemic changes observed. The results suggest that while nNOS expression may be modified in certain cells, iNOS is induced after a 2-4 h period, and that changes in protein nitration may be associated with changes in cell morphology.
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PMID:Neuronal and inducible nitric oxide synthase expression and protein nitration in rat cerebellum after oxygen and glucose deprivation. 1147 18


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