Role of Endothelium-Related Mechanisms in the Pathophysiology of Renal Ischemia/Reperfusion in Normal Rabbits

Abstract

The present study addressed the effect of interventions aimed to increase NO in the setting of acute renal ischemia/reperfusion (I/R) in uninephrectomized rabbits. In the 60-minute post-I/R period, l-arginine+superoxide (O₂^•−) dismutase (SOD) synergistically improved the renal functional (69.4% versus 10.4% of the pre-I/R glomerular filtration rate with or without l-arginine+SOD, respectively; P<.01) and histological parameters (82.9% decrease of medullary congestion in l-arginine+SOD, P<.01 versus vehicle) and blocked the I/R-dependent neutrophil accumulation (89.3% reduction). In spite of these results over the short term, a second set of experiments disclosed that the protection by l-arginine+SOD was no longer present at 24 and 48 hours (plasma creatinine in vehicle-treated versus l-arginine+SOD–treated animals [mg/100 mL]: 24 hours after I/R, 9.4±1.9 versus 8.07±0.65; 48 hours after I/R, 11.6±3.6 versus 9.7±0.9; P=NS in all the cases). Additional experiments were conducted using a milder 30-minute ischemic model, which showed no significant functional or histological protection by using l-arginine+SOD. In conclusion, our experiments disclosed the following: (1) the critical importance of the interaction between NO and O₂^•− in the acute protective effect of l-arginine (this effect not only improved renal function and histology but also reduced neutrophil accumulation) and (2) the discordance existing between the immediate protection afforded by l-arginine+SOD and the lack of protection observed at 24 and 48 hours. This finding suggests that a punctual intervention on the NO system at the time of I/R is not sufficient to reduce renal damage over the long term.