PROTECTIVE EFFECT OF N-ACETYL-L-CYSTEINE ON THE RENAL-FAILURE INDUCEDBY INFERIOR VENA-CAVA OCCLUSION

Background. Renal ischemia is produced during orthotopic liver transpl antation when the inferior vena cava is clamped above the renal veins (inferior vena cava occlusion [IVCO]), and it often leads to postopera tive renal failure. Although free radicals and nitric oxide (NO) have been implicated in the pathogenesis of ischemic renal failure, the eff ect of free radical scavengers in this model is unknown. Methods. The effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, on the acute renal failure that follows IVCO were evaluated in pentobarbital -anesthetized dogs. The effect of NO synthesis inhibition with N-G-nit ro-L-arginine methyl ester (NAME) was also studied. Renal vascular end othelial function was tested by infusing acetylcholine (Ach) into the renal artery before the ischemia and during reperfusion. Results. Rena l failure developed during IVCO and persisted during reperfusion in al l groups. However, in NAC-pretreated dogs, the glomerular filtration r ate recovered progressively, reaching 31% of basal preischemic values 150 min after reperfusion. During reperfusion, fractional excretion of sodium increased above preischemic values only in the control group, which indicates a beneficial effect of NAC and NAME on the tubular dys function observed during reperfusion. The renal response to Ach was ab olished in control dogs and in animals given NAME during reperfusion, which indicates endothelial dysfunction, However, in NAC-pretreated do gs, the renal response to Ach was preserved during reperfusion, Conclu sions. These results demonstrate that NAC ameliorates the renal failur e and renal endothelial dysfunction induced by IVCO. This protective e ffect was abolished by NAME, which suggests that NO is involved in the beneficial effects of NAC. These data also suggest that the use of NA C could be beneficial in ameliorating the acute renal failure observed after orthotopic liver transplantation.