Influence of nitric oxide on renal function in toxic acute renal failure in the rat

Besides other mechanisms, nitric oxide (NO) plays a major role in maintaining the high renal blood flow (RBF) and is also involved in the regulation of glomerular hemodynamics and contractility of mesangial cells. We examined the hypothesis that L-arginine-derived NO exerts beneficial effects in toxic acute renal failure (ARF) in the rat. To induce ARF uranyl nitrate (UN) was given intravenously as a bolus injection (25 mg/kg over 5 min) following a basal period. After the initiation phase of ARF (3 h) saline in the control group (C) and drugs in the experimental groups (I-III, each n = 8) were administered for 60 min. Group I: Arg (= L-arginine, 300 mg/kg), group II: MeArg (= N-methyl-L-arginine, 30 mg/kg), group III: Arg + MeArg (300 mg/kg, 30 mg/kg respectively). The experiments were continued for additional 60 min following the infusion period. Glomerular filtration rate (GFR, inulin clearance) was reduced 3 h after UN to about 50% of normal values in group I-III and control group. After infusion of Arg GFR had significantly improved, but remained unchanged after MeArg in relation to control. One hour after the infusion period these effects were even more pronounced. We conclude that NO exerts beneficial effects on renal function in this animal model of ARF. These results underline the regulatory role of the L-arginine/NO pathway for renal function not only under basal conditions but also in ARF.