ROLE OF ENDOTHELIUM-RELATED MECHANISMS IN THE PATHOPHYSIOLOGY OF RENAL ISCHEMIA REPERFUSION IN NORMAL RABBITS/

The present study addressed the effect of interventions aimed to incre ase NO in the setting of acute renal ischemia/reperfusion (I/R) in uni nephrectomized rabbits. In the 60-minute post-Im period, L-arginine+su peroxide (O-2(.-)) dismutase (SOD) synergistically improved the renal functional(69.4% versus 10.4% of the pre-I/R glomerular filtration rat e with or without L-arginine+SOD, respectively; P < .01) and histologi cal parameters (82.9% decrease of medullary congestion in L-arginine+S OD, P < .01 versus vehicle) and blocked the I/R-dependent neutrophil a ccumulation (89.3% reduction). In spite of these results over the shor t term, a second set of experiments disclosed that the protection by L -arginine+SOD was no longer present at 24 and 48 hours (plasma creatin ine in vehicle-treated versus L-arginine + SOD-treated animals [mg/100 mL]: 24 hours after I/R, 9.1 +/- 1.9 versus 8.07 +/- 0.65; 48 hours a fter I/R, 11.6 +/- 3.6 versus 9.7 +/- 0.9; P = NS in all the cases). A dditional experiments were conducted using a milder 30-minute ischemic model, which showed no significant functional or histological protect ion by using L-arginine+SOD. In conclusion, our experiments disclosed the following: (1) the critical importance of the interaction between NO and O-2(.-) in the acute protective effect of L-arginine (this effe ct not only improved renal function and histology but also reduced neu trophil accumulation) and (2) the discordance existing between the imm ediate protection afforded by L-arginine+SOD and the lack of protectio n observed at 24 and 48 hours. This finding suggests that a punctual i ntervention on the NO system at the time of I/R is not sufficient to r educe renal damage over the long term.