Blockade of the L-arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury.

摘要: Organ graft preservation injury is a major problem complicating liver transplantation. The L-arginine/nitric oxide pathway has protective effects in several models of injury. purpose this study was to evaluate the role L-arginine/NO synthase (NOS) on and characterize endogenous inducible NOS (iNOS) expression. Orthotopic transplantation performed with 18-hour University Wisconsin solution syngeneic rats. Recipient rats were either untreated or treated L-arginine, D-arginine, nonspecific inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), iNOS selective L-N(6)-(1-imino-ethyl)lysine (L-NIL) after revascularization. As early as 1 hour following reperfusion, circulating arginine levels decreased 10-fold ornithine increased 4-fold. A corresponding increase arginase I protein detected serum. To address profound deficiency, we supplemented recipients L-arginine (but not D-arginine) supplementation significantly reduced 12 hours suggesting that effect mediated through generation NO. expression peaked 6 reperfusion. Blockade L-NAME necrotic apoptotic cell death transplanted graft. Addition L-NIL mildly transaminase also apoptosis In conclusion, transplant are profoundly deficient postreperfusion due release. L-Arginine NO synthesis decrease ameliorate