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 main taining the high renal blood flow (RBF) and is also involved in the re gulation of glomerular hemodynamics and contractility of mesangial cel ls. We examined the hypothesis that L-arginine-derived NO exerts benef icial 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 p hase of ARF (3 h) saline in the control group (C) and drugs in the exp erimental groups (I-III, each n = 8) were administered for 60 min. Gro up I: Arg (= L-arginine, 300 mg/kg), group n: MeArg (=N-methyl-L-argin ine, 30 mg/kg), group III: Arg + MeArg (300 mg/kg, 30 mg/kg respective ly). The experiments were continued for additional 60 min following th e 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 improve d, 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 ARE These results underline the regulatory role of the L-arginine/NO pathway for renal function not only under basal conditi ons but also in ARE.