Introduction: In recent years, there are some reports on the involvement of iNOS (inducible form of nitric oxide synthase) in proteinuria associated with renal disease. Studies in models of acute renal failure (ARF) have yielded convincing evidence that iNOS can be induced during ischemia-reperfusion (IR) conditions and acute renal allograft rejection. The present study was designed to investigate the effect of L-Nil (N6-(1-Iminoethyl)-L- lysine hydrochloride), a selective inhibitor of iNOS, in prevention of renal proteinuria in IR injury.
Methods: Rats were randomly assigned in four groups of Sham-operated, Sham+L-Nil, IR and IR+L-Nil. Ischemic acute renal failure (ARF) was induced by 40-min clamping of the renal arteries followed by 6 h reperfusion. Rats were administered either L-Nil (3 mg kg-1 I.V. bolus followed by infusion of 1 mg kg-1 h-1) or saline. To monitor glomerular & tubular functional changes before and after treatment, BUN, plasma creatinine (Cr) and urinary NAG (N-Acetyl-b-D-glucosaminidase) activity were measured. Total protein, albumin, low and high molecular weight protein excretion rates were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of urine samples.
Results: Renal IR resulted in significant low and high molecular weight proteinuria. L-Nil significantly prevented the IR-induced increases in total protein, albumin and a1-microglobulin excretion.
Conclusion: This study suggests that iNOS inhibition reduces IR-mediated renal proteinuria.