Nitric oxide and superoxide in ishcemia/reperfusion injury

点击翻译按钮获取中文摘要

PURPOSE.To evaluate the role of nitric oxide in ischemia/reperfusion injury.METHODS.Experiment 1) Male Wistar rats (250-350 gin) were underwent intestinal ischemia for 30 minutes and reperfusion for 60 minutes. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), the substrate for NO generation, L-arginine (L-Arg, 300 mg/kg) or saline (5 ml/kg) were administered intravenously 10 minutes before ischemia. Arterial blood pressure, portal blood flow, hepatic- and intestinal-tissue blood flow were monitored as hemodynamic parameters during the procedure. Plasma reduced glutathione (GSH) and oxidized glutathione (GSSG) were investigated to evaluate oxidant stress at the end of the procedure. The damage of the resected specimen of the ileum was examined microscopically.Experiment 2) Ischmeia/reperfusion of the partial lobe of the liver in Male Wistar rats (250-350 gm) were perfumed. The L-NAME (20 mg/kg/h), the L-arginine (600 mg/kg/h) or saline (5 ml/kg/h) were con … More tineously administered intravenously 10 minutes before ischemia. Hepatic microvascular blood flow in the I/R non-I/R lobes were monitored as hemodynamic parameters during the procedure. GSH and GSSG in the I/R and non-I/R lobes were investigated to evaluate oxidant stress at the end of the procedure. The damage of the I/R lobe and non-I/R lobes was examined microscopically.RESULTS.The experiment 1 and 2 reveals that inhibition of NO production deteriorated organ blood flow exacerbated tissue destruction in IRI with increased oxidant stress. L-NAME treatment deteriorates microvascular circulation, increases mucosal damage. Moreover, inhibition of NO production aggravates oxidant stress in both acute intestinal ischemia/reperfusion model and partial hepatic ischemia/reperfusion model. In experiment 1, L-NAME-treated rats showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage and submucosal necrosis, while L-Arg-treated rats had low histopathologic grading of terminal ileal samples. The protective effect of L-arginine treatment on intestinal and partial hepatic ischemia/reperfusion injury may be related its ability to prevent microvascular constriction by the stimulation of endogenous NO production. Less