Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats

We investigated the effects of orally supplemented L-arginine, the substrat e of nitric oxide (NO) and N-omega-nitro-L-arginine methyl eater (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g /l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or ge ntamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group dev eloped marked renal failure, characterized by a significantly decreased cre atinine clearance and increased blood creatinine, fractional excretion of s odium, fractional excretion of lithium, urine gamma glutamyl transferase, s ystolic blood pressure and daily urine volume when compared to controls. Re nal histological analysis confirmed tubular necrosis. L-arginine administra tion caused normalization of these parameters, whereas L-NAME led to aggrav ation of the failure. Concomittant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to t he rats receiving gentamicin alone. We conclude that L-arginine supplementa tion has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME. (C) 2000 Elsevier Science B.V. All rights reserved.