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(Circulation Research. 1996;79:1031-1038.)
© 1996 American Heart Association, Inc.

Articles

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

C. Caramelo, G. Espinosa, F. Manzarbeitia, M.R. Cernadas, G. Perez Tejerizo, D. Tan, J.R. Mosquera, E. Digiuni, M. Monton, I. Millas, L. Hernando, S. Casado, A. Lopez-Farre

the Laboratorio de Nefrologia e Hipertension (C.C., M.R.C., G.P.T., D.T., J.R.M., E.D., M.M., I.M., L.H., S.C., A.L.-F.), Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain; the Universidade Federal de Rio de Janeiro (Brasil) (G.E.); and the Hospital de Mostoles (F.M.), Madrid, Spain.

Correspondence to A. Lopez-Farre, PhD, Laboratorio de Nefrologia e Hipertension, Fundacion Jimenez Diaz, Av. Reyes Catolicos 2, Madrid 28040, Spain.

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.

Key Words: L-arginine • superoxide dismutase • neutrophil • nitric oxide

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