Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been postulated that nitric oxide (NO) can react with superoxide anion (.O2-) to generate hydroxyl (.OH) radical. If this is correct, inhibition of NO synthesis could attenuate .OH radical mediated ischemia/reperfusion injury. Therefore we studied the effects of NG-nitro-L-arginine (L-NNA), a competitive inhibitor of the NO synthase enzyme on ischemia/reperfusion injury injury in isolated perfused rat hearts. Three groups of rats (n = 12-15) were studied. Group I: Untreated ischemia/reperfusion control (37.5 min of global ischemia followed by 20 min reperfusion); Group II: ischemia/reperfusion with 25 microM NG-nitro-L-arginine; and Group III: ischemia/reperfusion in the presence of L-NNA and 2 mM L-arginine, the substrate for NO synthase. Coronary flow (in ml/min) and ventricular developed pressure, +dP/dt and -dP/dt were measured 5 min prior to ischemia and at the end of reperfusion. Baseline preischemic developed pressure was significantly lower in L-NNA perfused hearts than controls (76.8 +/- 5.9 v 97.6 +/- 2.9 mmHg, P < 0.05). However, the developed pressure following reperfusion was significantly greater in L-NNA perfused hearts (57.4 +/- 7.4 v 20.8 +/- 6.4 mmHg in control). This protective effect was reversed by the addition of L-arginine. Preischemic coronary flow was decreased significantly in the L-NNA group (6.4 +/- 0.5 ml/min) compared to controls (11.6 +/- 0.7 ml/min). The duration of sinus rhythm was significantly improved from 3.8 +/- 1.2 min in controls to 15.1 +/- 0.8 min in L-NNA perfused hearts. A corresponding significantly lower incidence of arrhythmias was observed (10.2 +/- 1.5 in ischemia/reperfusion group v 1.7 +/- 0.8 min with L-NNA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained inhibition of nitric oxide by NG-nitro-L-arginine improves myocardial function following ischemia/reperfusion in isolated perfused rat heart. 776 Mar 62

Dopamine (DA) is released in large quantities from the striatum during cerebral ischemia. Along with excitatory neurotransmitters, DA plays a role in cellular neuronal ischemic injury. In this study we examined the role of nitric oxide (NO) in the ischemia-induced release of DA. A microdialysis probe was stereotactically placed into the corpus striatum of 16 Sprague-Dawley rats for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) level determinations. After probe stabilization, the animals received either NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, or vehicle through the microdialysis probe. Temporary global forebrain ischemia was induced using bilateral carotid artery ligature tightening and controlled hemorrhagic hypotension for 15 min. L-NAME administration caused a reduction in ischemic estimated extraneuronal DA concentration by 60% (P < 0.005) compared with control. There was an increase in both DOPAC and HVA concentrations during the recovery period compared to baseline values in the control group (P < 0.05). L-NAME also caused a reduction in HVA concentration compared to vehicle administration during the latter part of recovery (P < 0.05). These data support the concept that ischemic dopamine release may be mediated by NO. This NO-modulated DA release may contribute to the previously reported deleterious neurotoxic effects of NO during ischemia.
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PMID:Nitric oxide modulates dopamine release during global temporary cerebral ischemia. 776 37

The cardioprotective effect of angiotensin-converting enzyme (ACE) inhibitors in cardiac ischemia/reperfusion damage is assumed to result largely from inhibition of the enzymatic breakdown of endogenous bradykinin (BK). We assessed the role of nitric oxide (NO) in mediating the beneficial actions of BK and the possible mechanism of the effect of NO. We experimentally infringed myocardial function in a working guinea pig heart preparation by ischemia (15 min) and reperfusion. The parameter external heart work (EHW), determined before and after ischemia, served as criterion for quantitation of recovery. We assessed oxidative stress during reperfusion by measuring glutathione release in coronary venous effluent; lactate release was used as a measure of ischemic challenge. The principal ability of NO to scavenge oxygen radicals was separately investigated in a chemiluminescence (CL) assay with the NO-donor sodium nitroprusside (SNP) and lucigenin. The ACE inhibitor ramiprilat (RT 25 microM) improved postischemic function significantly (55% recovery of EHW vs. 29% for controls). BK 1 nM was even more cardioprotective (71% recovery). The NO-synthase inhibitor Ng-nitro-L-arginine (NOLAG 10 microM) inhibited the effects of RT and BK (18% recovery each). SNP (0.3 microM) improved recovery to 57%, the prostacyclin analogue iloprost (ILO, 0.1 and 3 nM) had no beneficial effect (21 and 20% recovery, respectively). With 8-bromo-cyclicGMP, a membrane-permeable cGMP analogue, function was not better than control (30% recovery). Release of glutathione during reperfusion was decreased by the three compounds known to increase NO concentration in the heart; lactate release was the same in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide accounts for postischemic cardioprotection resulting from angiotensin-converting enzyme inhibition: indirect evidence for a radical scavenger effect in isolated guinea pig heart. 776 10

Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.
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PMID:Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. 777 69

Nitric oxide, NO., exerts numerous important regulatory functions in biological tissues and has been hypothesized to have a role in the pathogenesis of cellular injury in a number of diseases. It has been suggested that alterations in NO. generation are a critical cause of injury in the ischemic heart. However, the precise alterations in NO. generation which occur are not known, and there is considerable controversy regarding whether myocardial ischemia results in increased or decreased NO. formation. Therefore, electron paramagnetic resonance studies were performed to directly measure NO. in isolated rat hearts subjected to global ischemia, using the direct NO. trap Fe(2+)-N-methyl-D-glucamine dithiocarbamate, which specifically binds NO. giving rise to a characteristic triplet EPR spectrum with g = 2.04 and aN = 13.2 G. While only a small triplet signal was observed in normally perfused hearts, a 10-fold increase in this triplet EPR spectrum was observed after 30 min of ischemia indicating a marked increase in NO. formation and trapping. Measurements were performed as a function of the duration of ischemia, and it was determined that with increased duration of ischemia NO. formation and trapping was also increased. NO. generation was inhibited by the nitric oxide synthase blocker, N-nitro-L-arginine methyl ester (L-NAME), suggesting that NO. was generated via nitric oxide synthase. Blockade of NO. generation with L-NAME resulted in more than a 2-fold increase in the recovery of contractile function in hearts reperfused after 30 min of global ischemia. Thus, ischemia causes a marked duration-dependent increase of NO. in the heart which may in turn mediate postischemic injury.
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PMID:Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy. 781 91

The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.
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PMID:Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor. 783 88

Endogenous nitric oxide which is enzymatically formed by endothelial cells from L-arginine has been implicated in the control of gastrointestinal circulation. Its role in the mediation of gastric tissue oxygenation has not been studied. We investigated the role of NO in the control of gastric blood flow and oxygen uptake. In anesthetized dogs, total gastric blood flow, gastric mucosal blood flow, systemic arterial and portal venous pressures and the arteriovenous oxygen content difference were studied. From these measurements gastric vascular resistance and oxygen consumption were calculated. Administration of NG-nitro-L-arginine (L-NNA) induced gastric tissue ischemia and hypoxia. Both, systemic arterial pressure and gastric vascular resistance were increased. Above hemodynamic and metabolic effects of L-NNA were significantly attenuated when administration of L-NNA was combined with L-arginine. Our findings suggest that endogenous NO is a tonic vasodilator modulating gastric blood flow and oxygen uptake through influence on the gastric microcirculatory structures responsible for vascular resistance and the nutrient circulation.
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PMID:Nitric oxide is involved in the mediation of gastric blood flow and tissue oxygenation. 784 49

The role of eicosanoid metabolism and its relationship with nitric oxide production in the ischemia-reperfusion associated with pancreas transplantation in the rat is explored in this study. Twenty-six male Sprague-Dawley rats were randomized into 3 groups, as follows: group 1, control animals not surgically manipulated; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 but with administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) (10 mg/kg) before organ revascularization. The results show posttransplantation increases in edema and in 6-keto-prostaglandin F1 alpha (x1.9), thromboxane B2 (x4), and prostaglandin E2 (x5) levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in edema and eicosanoid production, which suggests that eicosanoid generation in the recipient rat would be mediated, in part, through a nitric oxide-dependent mechanism.
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PMID:Nitric oxide and arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation. 787 73

Inhibition of nitric oxide synthase with nitro-L-arginine (i.p., 40 mg/kg body weight) in contrast to L-arginine (300 mg/kg body weight) delayed the initial recovery of cerebral blood flow (CBF) and altered dopamine (DA) metabolism in brain ischemia/reperfusion of Mongolian gerbils. Similar changes but more severe were observed with pargyline (monoamine oxidase inhibitor). Data suggest nitric oxide involvement in postischemic CBF recovery and modulation of DA metabolism due to nitro-L-arginine-induced CBF reduction.
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PMID:Effect of nitro-L-arginine on cerebral blood flow and monoamine metabolism during ischemia/reperfusion in the mongolian gerbil. 789 28

Coronary artery endothelium exhibits functional impairment after ischemia and reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (60 minutes) through a left internal mammary artery graft. In organ chamber experiments, control (left circumflex coronary artery) and reperfused (left anterior descending coronary artery) arterial segments were contracted with prostaglandin F2 alpha and exposed to hypoxia (oxygen tension = 35 +/- 5 mm Hg). Reperfused coronary rings with endothelium exhibited contractions to hypoxia that were significantly greater than contractions in control rings with endothelium (+78% +/- 8% and +14% +/- 5%, respectively; p < 0.05). This phenomenon could be blocked by NG-monomethyl-L-arginine. Electron microscopic studies showed platelet adhesion and aggregation, denudation of the endothelium and disruption of the intercellular junctions, edematous subendothelial matrix, and vesiculation of the smooth muscle cells in reperfused LAD. Swelling, vacuole formation, and loss of neurofilament occurred in the nerve fibers accompanying the vessels. These phenomena were not observed in control vessels. This study demonstrates that early after coronary artery bypass grafting, hypoxia can induce coronary vasospasm mediated by an L-arginine-dependent metabolic pathway in the endothelium. The ultrastructural changes in the coronary endothelium include platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle. The endothelium-dependent hypoxic coronary vasospasm and ultrastructural changes in the coronary endothelium may play an important role in the pathogenesis of myocardial ischemia and infarction after coronary artery bypass grafting.
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PMID:Acute endothelial reperfusion injury after coronary artery bypass grafting. 794 3


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