INHIBITION OF NITRIC-OXIDE SYNTHESIS AGGRAVATES HEPATIC OXIDATIVE STRESS AND ENHANCES SUPEROXIDE-DISMUTASE INACTIVATION IN RATS SUBJECTED TO TOURNIQUET SHOCK

The role of nitric oxide (NO) on liver oxidative stress and tissue inj ury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote o rgan damage. Liver oxidative stress becomes evident after hind limb re perfusion, as evidenced by the loss of total tissue thiols; by increas es in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), pl asma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in tot al superoxide dismutase (SOD) activity. Portal blood flow is reduced b y 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with N-omega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure further reduced portal blood f low; and aggravated liver injury as assessed by further loss in total thiols, Increased LPO and GSSG content, and further increases in plasm a ALT and AST. Total plasma nitrites were lower than in control animal s, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in porta l blood flow and also reverted tissue thiol loss, LPO, and GSSG increa ses, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.