UMLS:C0406810 - FACTA Search

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

We have compared the myocardial alterations in rats made hypertensive by the chronic inhibition of nitric oxide biosynthesis with those having renal hypertension (two kidney-one clip model). Male Wistar rats were chronically administered the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) for 2, 4 and 8 weeks. Both groups initially developed a similar increase in blood pressure but only the 2K-1C rats developed myocardial hypertrophy after 2-4 weeks. L-NAME-treated animals developed a similar degree of hypertrophy following 8 weeks of treatment. As observed by light microscopy, the myocardial alterations in the latter animals consisted of extensive areas of fibrosis and myocardial necrosis, especially in regions of the subendocardium. The histological alterations induced by L-NAME were not caused by the accompanying hypertension, since the 2K-1C animals had a similar increase in arterial blood pressure without any significant alterations in the heart morphology. 2K-1C rats treated chronically with L-NAME behaved in a manner similar to the L-NAME-treated animals with regard to both the blood pressure increases and cardiac morphological alterations. Animals which received the inactive enantiomer D-NAME did not develop hypertension nor did they have any morphological abnormalities. Both the coronary flow and the contractile capacity of hearts isolated from rats treated with L-NAME for 8 weeks were impaired compared to control animals. These results indicate that the chronic inhibition of NO biosynthesis causes cardiac ischemia associated with a mechanical dysfunction that is unrelated to cardiac hypertrophy which is similar to those seen in some patients suffering from chronic arterial hypertension.
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PMID:Chronic nitric oxide inhibition as a model of hypertensive heart muscle disease. 883 44

Partial ischemia of rat pancreas body and tail was obtained by occlusion of the celiac axis for 1 h after gastrectomy. The plasma level of nitrite plus nitrate in both systemic and portal venous blood after reperfusion was significantly higher than that after sham operation and ischemia alone. The elevation after reperfusion was significantly decreased by NG-nitro-L-arginine methyl ester (L-NAME). Simultaneous administration of L-arginine counteracted the L-NAME-induced decrease in the level of nitric oxide (NO) end products. Generation of NO was further demonstrated by nitrosylhemoglobin detection by electron spin resonance in the blood after reperfusion. On the other hand, the plasma level of lipase, a marker of damage to pancreatic exocrine tissue, was significantly increased after ischemia-reperfusion and further increased by administration of L-NAME. This increase in lipase correlated with a decrease in tissue blood flow in the pancreas. These results suggest that NO is generated during and may have a protective role in ischemia-reperfusion of the rat pancreas.
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PMID:Detection of nitric oxide production and its role in pancreatic ischemia-reperfusion in rats. 884 62

Reactive oxygen species such as nitric oxide (NO) and/or superoxide have been proposed as mediators in the pathogenesis of reperfusion injury and acute endotoxemia. The purpose of this study was to examine the role of NO in a model of hepatic ischemia-reperfusion with endotoxemia (I/R + LPS). Rats subjected to 30 min of partial hepatic ischemia followed by reperfusion and LPS (Salmonella enteritidis, 1 mg/kg, i.v.,) administration, exhibited a marked, time-dependent increase in plasma alanine aminotransferase (ALT) levels compared to sham controls. An abrupt increase in liver nitrite/nitrate levels was also observed in I/R + LPS rats in association with the increases in plasma ALT. Although liver NO production in I/R + LPS rats increased with time, exacerbation of liver damage was not evident. Administration of L-NAME decreased NO production in plasma and liver but did not affect the liver damage in rats subjected to I/R + LPS. Superoxide levels in livers from I/R + LPS rats increased by threefold after 90 min reperfusion as compared to sham controls but dropped to control levels after 4 hr. There was a significant increase in neutrophils in liver lobes subjected to ischemia-reperfusion and LPS compared to sham controls and to non-ischemic lobes which received LPS. The number of neutrophils in the liver increased further in rats given L-NAME. These results suggest that the progressive injury seen in livers of I/R + LPS rats was possibly due to NO interaction with superoxide forming another reactive oxygen species such as peroxynitrite. However, inhibition of NO synthesis did not ameliorate liver damage, possibly because of an increase in tissue accumulation of activated polymorphonuclear leukocytes (PMN). Lung NO production increased in I/R + LPS rats after 4 hr reperfusion compared to sham controls. Prior administration of L-NAME did not prevent a significant rise in pulmonary NO generation (P < 0.05 at 90 min and 4 hr, compared to sham controls). This unexpected rise of pulmonary NO in the L-NAME treated group of rats was associated with a tendency for increased PMN accumulation (based on myeloperoxidase data) and superoxide generation. The results suggest that endogenous NO protected against excessive neutrophil infiltration in the lung in this model of hepatic ischemia-reperfusion and endotoxemia, and the use of L-NAME, a nonselective NOS inhibitor, may aggravate lung injury.
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PMID:Role of nitric oxide in hepatic ischemia-reperfusion with endotoxemia. 884 95

We have previously reported that we have observed chronic pain-like response to light mechanical stimuli (allodynia) in rats after severe spinal cord ischemia, which resembles some painful conditions in chronic spinally injured patients and is not relieved by a number of conventional analgesics used for treating chronic neuropathic pain. In the present study, we tested the effects of the non-selective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS inhibitor 7-nitro indazole (7-NI) and 6-nitro indazole (6-NI) on the chronic allodynia-like behavior. Systemic L-NAME dose-dependently relieved mechanical allodynia-like response in a stereo-specific and L-arginine-reversible manner without causing sedation or motor deficits. However, L-NAME significantly elevated systemic blood pressure. Systemic 7-NI relieved chronic allodynia in a L-arginine reversible manner, did not increase blood pressure or induce sedation, but caused motor deficits at a high dose, which was not reversed by L-arginine. Systemic 6-NI also relieved the chronic allodynia, which was however associated with severe sedation. In order to exclude the possibility that the effect of L-NAME on blood pressure was involved in the analgesic effect observed, the effect of systemically applied adrenaline was examined. Adrenaline increased the systemic blood pressure to a similar extent as L-NAME, but did not relieve allodynia. It is suggested that blockade of NOS by L-NAME relieved the chronic allodynia-like behavior in spinally injured rats. This effect was likely to be mediated by a blockade of neuronal isoforms of NOS, as 7-NI relieved the allodynia in a L-arginine-reversible manner. Consequently, generation of NO by neuronal NOS may be critically involved in the maintenance of this abnormal pain-related sensation. The possibility of using NOS inhibitors as potential novel analgesics is discussed.
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PMID:Treatment of a chronic allodynia-like response in spinally injured rats: effects of systemically administered nitric oxide synthase inhibitors. 888 Aug 55

During cerebral ischemia, nitric oxide (NO) production via stimulation of NO synthase, is likely one of the major events leading to neuronal death. Recently, we have demonstrated that after reversible focal ischemia, apoptosis was implicated in the penumbra whereas necrosis was prominent in the ischemic core. We have now examined the effect of a non-specific inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME, 3 ing kg-1 i.p., 5 min and 3 h after the onset of ischemia), on the progress of apoptotic and necrotic nuclei following transient focal cerebral ischemia, using DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL assay). Our results indicated that L-NAME prevented the loss of necrotic, but not apoptotic cells.
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PMID:NG-nitro-L-arginine methyl ester reduces necrotic but not apoptotic cell death induced by reversible focal ischemia in rat. 888 9

Nitric oxide (NO) is considered to be associated with the pathogenesis of cerebral ischemic injury. In the present study, NO production was continuously monitored employing in vivo microdialysis. A microdialysis probe was inserted into the stratum. Levels of the major NO metabolite, NO-2, in the dialysate were determined using the Griess reaction. Rats were subjected to global cerebral ischemia produced by occlusion of both common carotid arteries together with induced hypotension. Cerebral ischemia induced a decrease in NO production, which was interrupted by a transient increase in NO synthesis. This increment was abolished in the presence of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), suggesting that NO synthase activity is transiently activated during ischemia. Following reperfusion, NO synthesis was enhanced. To our knowledge, this is the first report concerning the continuous temporal profile of NO production during global cerebral ischemia and reperfusion.
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PMID:Brain nitrite production during global ischemia and reperfusion: an in vivo microdialysis study. 889 12

To investigate the role of superoxide in the toxicity of nitric oxide (NO), we examined the effect of nitric oxide synthase (NOS) inhibition on brain infarction in transgenic mice overexpressing CuZn-superoxide dismutase (SOD-1). Male SOD-transgenic mice and non-transgenic littermates (30-35 g) were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Either NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg), a mixed neuronal and endothelial NOS inhibitor, or 7-nitroindazole (7-NI; 25 mg/kg), a selective neuronal NOS inhibitor, was administered intraperitoneally 5 min after the onset of ischemia. At 24 h of reperfusion, the mice were decapitated and the infarct volume was evaluated in each group. In the nontransgenic mice, L-NAME significantly increased the infarct volume as compared with the vehicle, while 7-NI significantly decreased it. In the SOD-transgenic mice, L-NAME-treated animals showed a significantly larger infarct volume than vehicle-treated ones, whereas there were no significant differences between 7-NI- and vehicle-treated mice. Our findings suggest that selective inhibition of neuronal NOS ameliorates ischemic brain injury and that both neuronal and endothelial NOS inhibition may result in the deterioration of ischemic injury due to vasoconstriction of the brain. Since L-NAME increased infarct volume even in SOD-transgenic mice, the protective effect of SOD could result from the vasodilation by increased endothelial NO as well as the reduction of neuronal injury due to less production of peroxynitrite compared to wild-type mice. Moreover, the neurotoxic role of NO might not be dependent on NO itself, but the reaction with superoxide to form peroxynitrite, because of no additive effects of SOD and a neuronal NOS inhibitor.
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PMID:Effects of nitric oxide synthase inhibition on brain infarction in SOD-1-transgenic mice following transient focal cerebral ischemia. 889 87

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

Nitric oxide (NO) is an endogenous protectant against reperfusion-induced ventricular fibrillation (VF) in the rat isolated heart. Here, the following were investigated: (1) the tissue source of cardioprotective NO using a novel inhibitor (7-nitro indazole; 7-NI) of the neuronal form of NO synthase (NOS) and direct detection of coronary effluent NO by chemiluminescence; and (2) the species dependence by comparing rat and rabbit hearts. Perfusion with modified Krebs solution was followed by 60 min left regional ischemia and 10 min reperfusion. 7-NI (1 microM) increased the incidence of VF from 0% to 60% in rat hearts (n = 10; P < 0.05). Co-perfusion with L-arginine (1 mM) reduced VF incidence to 20% (P:N.S. v controls). The inactive analog of 7-NI (6-amino indazole: 6-AI) had no pro-fibrillatory activity. Neither 7-NI nor 6-AI affected coronary flow or recovery of flow during reperfusion. 7-NI reduced basal coronary effluent NO levels to below the limit of detection (< 1 pmol), but a massive increase in NO levels occurred when L-arginine was co-perfused with 7-NI. Although 7-NI had no effect on basal coronary flow and, by implication, resting NO release, it was found, in separate studies, to antagonise substance P-induced vasodilatation and NO release, suggesting that its neuronal selectivity is lost in the presence of an exogenously administered activator of endothelial NOS in rat hearts. In rabbit hearts, in contrast, 7-NI had no effect on VF or NO levels. However, in rabbit hearts the isozyme non-selective NO synthase blocker, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM), increased VF incidence from 0 to 50% (P < 0.05) and, during the first minute of reperfusion, reduced NO levels from 4929 +/- 893 to 2505 +/- 483 pmol/min/g (P < 0.05) and recovery of coronary flow by 22% (P < 0.05). Each of these effects were prevented by L-arginine co-perfusion. These data indicate a role for basally released NO as an endogenous antifibrillatory cardioprotectant in rat and rabbit isolated heart and indicate that the tissue source (neuronal in rat but not in rabbit heart) is species-dependent.
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PMID:Endogenous protection against reperfusion-induced ventricular fibrillation: role of neuronal versus non-neuronal sources of nitric oxide and species dependence in the rat versus rabbit isolated heart. 893 Aug 5

Nitric oxide (NO) protects the heart against some forms of reperfusion-associated dysfunction (e.g. arrhythmias). Its role in protecting against other types of dysfunction is controversial. NO ameliorates polymorphonuclear cell-induced exacerbation of stunning. Here, whether endogenous NO protects against contractile dysfunction in a polymorphonuclear cell-free model has been tested. Isolated rat hearts (n = 6 per group) were perfused with Krebs solution for 15 min. They were then perfused with test solution: Krebs, or Krebs containing 100 microM NG-nitro-L-arginine methyl ester (L-NAME) (a concentration shown previously to significantly reduce NO content in coronary effluent), 100 microM L-NAME plus 10 mM L-arginine (the latter shown previously to be sufficient to surmount the effect of L-NAME), or 10 mM L-arginine alone. After 10 min of this, the hearts were subjected to 60-min normothermic global ischemia followed by reperfusion with the same test solution as before. A time-matched (sham) group was perfused continuously with Krebs. L-NAME hastened the onset of ischemic contracture (P < 0.05) and increased its peak value from 67.8 +/- 4.6 mmHg to 93.0 +/- 4.9 mmHg (P < 0.05). Both effects were prevented by co-perfusion with 10 mM L-arginine. Initially, reperfusion exacerbated diastolic contracture, but diastolic pressure at a constant ventricular volume fell from 112 +/- 27 mmHg to 73 +/- 19 mmHg between the 5th and 60th min of reperfusion in drug-free hearts, indicative of recovery from diastolic stunning. This recovery was not exacerbated or lessened by perfusion with L-NAME or L-arginine. Left ventricular developed pressure increased from 42 +/- 2 mmHg to 106 +/- 18 mmHg in controls between 5 and 30 min after the start of reperfusion, the latter value being indistinguishable from that in the sham group. At this time, the value in the L-NAME group was similar (78 +/- 18 mmHg). This indicated complete recovery from systolic stunning in both groups 30 min after the start of reperfusion. However, earlier after the start of reperfusion, there had been zero pressure development in the L-NAME group (P < 0.05 v the control group). This was associated with severe impairment of recovery of coronary flow, e.g. of only 18% of the mean coronary flow in controls 5 min after the start of reperfusion (P < 0.05). At 30 min after the start of reperfusion (when systolic function had recovered in the L-NAME group), flow recovery had increased in this group to 96% of the mean control values. The impairment in rates of recovery of systolic function and coronary flow in the L-NAME group were each prevented by coperfusion with L-arginine (P < 0.05). In conclusion, endogenous NO may delay the onset and reduce the magnitude of ischemic contracture but despite this, appears not to facilitate early recovery from systolic and diastolic stunning as a result of any direct action in the myocardium. The beneficial effect it does possess in this polymorphonuclear cell-free preparation is transient and results from mediation of rapid recovery of coronary flow during reperfusion.
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PMID:Effect of endogenous nitric oxide on cardiac systolic and diastolic function during ischemia and reperfusion in the rat isolated perfused heart. 893 Aug 6

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