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)

Aortic occlusion and revascularization (I-R) may lead to lung injury dependent on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of increasing or decreasing NO levels with sodium nitroprusside (SNP) or N-nitro-L-arginine methyl ester (L-NAME) in an I-R lung injury model of 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats (10/group) were randomized to controls, I-R, I-R treated with L-NAME (10 mg/ml/hr), and I-R treated with SNP (0.2 mg/ml/hr). Myeloperoxidase activity (MPO) was used as a measure of pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio and bronchoalveolar lavage protein (BAL prot) and neutrophil counts (BAL PMN). Aortic occlusion and revascularization led to significant increases in pulmonary neutrophil influx (6.1 +/- 0.1 MPO u/g vs 3.05 +/- 0.4 MPO u/g in the control group, P < 0.001) and microvascular leakage; BAL prot (347 +/- 32 mg/ml in controls vs 454 +/- 16 mg/ml in the I-R group, P < 0.05); and BAL PMN (0.7 +/- 0.05 in controls vs 1.8 +/- 0.07 PMN/ml in the I-R group, P < 0.001). These changes were exacerbated further by administration of L-NAME (MPO = 8.9 +/- 0.7; BAL prot = 581 +/- 40 mg/ml; BAL PMN = 2.7 +/- 0.16 PMN/ml). Sodium nitroprusside therapy attenuated the I-R-induced lung injury (3.5 +/- 0.4 MPO u/g, P < 0.05 vs I-R; BAL prot = 330 +/- 61 mg/ml; BAL PMN = 0.9 +/- 0.1 PMN/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide (endothelium-derived relaxing factor) attenuates revascularization-induced lung injury. 804 Nov 46

We tested the hypothesis that decreased tonic release of nitric oxide (NO) or a NO-containing compound, during postischemic delayed hypoperfusion, would result in an impaired response of cerebral blood flow (CBF) to NO synthase inhibition. We measured CBF (microspheres), cerebral oxygen consumption, and physiological variables in 30 halothane-anesthetized cats. In 12 animals, complete cerebral ischemia (verified by midischemic CBF measurement) was produced for 12 min by brachiocephalic and left subclavian artery occlusion with hemorrhagic hypotension (mean arterial blood pressure = 40 mmHg). Steady-state hypoperfusion was present by 120 min of reperfusion (30 +/- 4% of baseline). Nonischemic animals (n = 12) were submitted to the same surgical procedures and anesthetic duration. N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv) or saline was administered 160 min after baseline measurements, equivalent to 140 min of reperfusion for animals treated with ischemia (n = 6 in each group). Blood pressure was controlled (aortic ligature) so that there was no change following L-NAME administration both in the ischemic and nonischemic groups. L-NAME reduced CBF during reperfusion in ischemic animals (from 37 +/- 2 to 24 +/- 2 ml.min-1 x 100 g-1) and in nonischemic animals (from 122 +/- 15 to 68 +/- 8 ml.min-1 x 100 g-1) with no change in cerebral oxygen consumption. In six additional cats, administration of L-arginine (250 mg/kg iv) reversed the effect of L-NAME. We conclude that tonic NO-mediated cerebral vasodilation occurs following transient global ischemia despite delayed hypoperfusion.
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PMID:Cerebral blood flow is reduced by N omega-nitro-L-arginine methyl ester during delayed hypoperfusion in cats. 804 83

The role of nitric oxide (NO) in ischemic neuronal injury is unclear. In permanent focal ischemia models, NO release has been reported to be both neuroprotective, by virtue of actions to improve cerebral blood flow (CBF) within ischemic tissue, and neurotoxic. Very little attention has been given to determining the role of NO in transient focal ischemia. In the present studies, low-dose NO inhibition using NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg/kg bolus, 0.01 mg.kg-1.min-1 iv) reduced infarct volume after 180 min of middle cerebral arterial occlusion (MCAO) and 120 min of reperfusion as measured via 2,3,5-triphenyltetrazolium chloride by 55% (P < 0.0001). Similar reductions occurred whether L-NAME was given throughout MCAO-reperfusion or just 30 or 60 min before reperfusion. L-NAME reduced CBF in the area of infarction at 30 and 180 min of MCAO by 36 and 33% (P < 0.02). In contrast, 15 min into reperfusion, L-NAME increased CBF in the area of infarction by 69% (P < 0.03) and by 27% in the contralateral homologous right hemisphere. Although vascular effects are present, these findings suggest a neurotoxic role for NO primarily during reperfusion after transient focal ischemic injury.
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PMID:Dual effects of L-NAME during transient focal cerebral ischemia in spontaneously hypertensive rats. 804 92

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.
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PMID:Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. 820 52

In a variety of recent studies, inhibitors of nitric oxide (NO) synthesis have ameliorated neuronal injury during permanent focal cerebral ischemia, suggesting that NO may contribute to ischemic damage. In other studies, however, these inhibitors increased infarct volume during permanent middle cerebral artery occlusion (MCAO). One complication in these studies was that high-dose NO synthase inhibitors increased mean arterial blood pressure (MAP) by 20-30 mm Hg. Thus, it is possible that variations in the effects of NO synthesis inhibitors on infarct volume could be related to effects of these inhibitors on MAP and cerebral perfusion during or after ischemia. The present study compared the effects of control (Ringer's lactate solution) versus low-dose NO inhibition (0.1 mg/kg bolus followed by 0.01 mg/kg/min) on cerebral infarct volume using L-NAME (NG-nitro-L-arginine methyl ester) administered during a 1-h baseline period, 3-h of MCAO, and 2 h of reperfusion in the spontaneously hypertensive rat. Infarct volume was determined using the TTC (2,3,5-triphenyltetrazolium chloride) method performed 5 h after onset of occlusion. L-NAME reduced infarct volume by 55%. In the control group (n = 7), infarct volume measured 116 +/- 4 (SEM) mm3 which was 29 +/- 1% of the left hemispheric volume (400.5 +/- 0.3 mm3). In the L-NAME group (n = 7), infarct volume measured 53 +/- 8 mm3 which was only 13 +/- 2% of the left hemispheric volume (400.4 +/- 0.5 mm3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low dose L-NAME reduces infarct volume in the rat MCAO/reperfusion model. 825 13

The present study tested the hypothesis that nitric oxide production in coronary resistance vessels is an important mechanism affecting the regulation of myocardial perfusion in unanesthetized dogs. We inhibited nitric oxide synthesis with the arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) and maintained the compressive determinants of myocardial blood flow constant by ventricular pacing. L-NAME did not affect resting coronary blood flow and reduced the receptor-mediated increase in flow to intracoronary acetylcholine (100 micrograms/min IC) from 143 +/- 20% (mean +/- SEM) under control conditions to 31 +/- 10% after L-NAME (P < .001). Coronary autoregulatory relations were determined as steady-state coronary pressure was reduced by inflating a hydraulic occluder. Initial resistance adjustments over the autoregulatory plateau were not affected by L-NAME. Closed-loop autoregulatory gain was 0.84 +/- 0.09 under control conditions versus 0.78 +/- 0.07 after L-NAME (P = NS). As coronary pressure was reduced further, however, the critical pressure at which myocardial ischemia began (lower autoregulatory break point) increased from 45 +/- 3 mm Hg under control conditions to 61 +/- 2 mm Hg (P < .001) after L-NAME. In addition, the slope of the coronary pressure-flow relation below the autoregulatory break point was reduced (1.0 +/- 0.2 versus 0.58 +/- 0.09 mL.min-1.mm Hg-1 after L-NAME, P < .05), reflecting a reduction in the maximal conductance recruitable during ischemia. In concert with the effects of L-NAME on autoregulatory responses during ischemia, peak reactive hyperemic flow to a 30-second coronary occlusion was also reduced (from 200 +/- 22 to 166 +/- 24 mL/min after L-NAME, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of coronary autoregulatory responses by nitric oxide. Evidence for flow-dependent resistance adjustments in conscious dogs. 833 Mar 72

The effects of 1 h of coronary arterial occlusion (CAO) followed by 15 min reperfusion (CAR) were examined in nine conscious dogs. Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different. However, adenylyl cyclase activity and the guanine nucleotide stimulatory protein (Gs) were reduced in ischemic subendocardium compared with nonischemic subendocardium. The fraction of beta-adrenergic receptors binding agonist with high affinity increased in ischemic subendocardial and subepicardial layers. Compared with prior data in experiments with 1 h CAO without CAR, the increase in beta-adrenergic receptor density that occurs with myocardial ischemia is rapidly reversed with CAR of 15 min duration, while the decreased fraction of receptors binding agonist with high affinity was reversed to an increase in high-affinity receptors. The global decreases in adenylyl cyclase and Gs, which have been observed with simple CAO, persist but are observed selectively in the previously ischemic subendocardium after CAR. Thus both CAO and CAR affect beta-adrenergic receptors and adenylyl cyclase differently. During CAR, increased numbers of beta-adrenergic receptors binding agonist with high affinity occur potentially as a compensatory mechanism in the face of persistent reductions in adenylyl cyclase activity and Gs.
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PMID:Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling. 838 10

The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.
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PMID:Ischemia-reperfusion in feline small intestine: a role for nitric oxide. 843 Jul 97

Using microdialysis, we evaluated temporal changes in striatal extracellular cGMP level following ischemia and its relationship to nitric oxide (NO) production. In untreated animals, significant elevation of cGMP was observed during ischemia and during 4 h of recirculation. In animals treated with L-NAME ischemia induced a modest increase in the cGMP level, but this level was significantly lower than that observed in the untreated animals. These results demonstrate first, that the microdialysis technique can be used to detect changes in extracellular cGMP levels during ischemia and second, that ischemia and recirculation induce a rise in cGMP which is diminished by nitric oxide synthase inhibition, suggesting a linkage to NO production.
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PMID:Ischemia-induced changes in extracellular levels of striatal cyclic GMP: role of nitric oxide. 854 96

The potential role of nitric oxide (NO) was investigated in the pathophysiology of liver injury after priming with 20 min hepatic ischemia-reperfusion and administration of .5 mg/kg Salmonella enteritidis endotoxin. Liver injury during the early reperfusion phase of 4 h was characterized by severe vascular oxidant stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of the microvascular blood flow in the liver. Inhibition of NO synthesis with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) aggravated liver injury by 90%, reduced LPO, and did not affect liver neutrophils but further impaired microvascular blood flow. Treatment with the NO-donor spermine-NONOate or L-arginine did not affect these parameters in postischemic animals, however, treatment did restore all values of L-NAME-treated animals back to disease control levels. These data suggest that endogenous NO formation is sufficient to limit ischemic liver injury during reperfusion but inhibition of NO synthesis will result in additional ischemic damage. NO may also be involved in scavenging of superoxide in the vasculature and in inducing LPO.
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PMID:Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic ischemia and endotoxemia. 856 57


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