TOXIC ACUTE-RENAL-FAILURE IN THE RAT - EFFECTS OF L-ARGININE AND N-METHYL-L-ARGININE ON RENAL-FUNCTION

Nitric oxide (NO) is generated from L-arginine (Arg) by different isof orms of nitric oxide synthase (NOS) and plays a major role in maintain ing the hi basal renal blood flow. NO also is involved in th regulatio n of glomerular haemodynamics and contractility of mesangial cells. We examined the hypothesis that L-arginine-derived NO modifies toxic ARF in the rat. After a basal period uranyl nitrate (UN) was given intrav enously as a bolus injection (25 mg/kg over 5 min) to induce ARF. Afte r the initiation phase of ARF (3 h) saline in the control group (C) an d drugs in the experimental groups (I-III, each n=8) were administered for 60 min. Group I, Arg (300 mg/kg); group II, MeArg (30 mg/kg); gro up III, Arg+MeArg (300 mg/kg, 30 mg/kg resp.). The experiments were co ntinued for further 60 min following the infusion period. Glomerular f iltration rate (GFR, inulin clearance) was reduced 3 h after UN to abo ut 50% of normal values in groups I-Ill and control group (I, 0.52+/-0 .06; II, 0.51+/-0.05; III, 0.49+/-0.05; C, 0.50+/-0.07 ml/min). After infusion of Arg GFR had significantly improved (0.64+/-0.07), but furt her declined after MeArg (0.46+/-0.06) in relation to control (0.47+/- 0.07). This negative effect could be overcome by combined administrati on of Arg+MeArg (0.59+/-0.07). One hour after the infusion period thes e effects were even more pronounced (Arg, 0.71+/-0.06; MeArg, 0.43+/-0 .05; Arg+MeArg, 0.65+/-0.07; C, 0.46+/-0.05). We conclude that the L-a rginine/NO pathway is involved in toxic ARF of the rat. NO exerts bene ficial effects on renal function in this animal model of ARF, whereas the competitive NOS inhibitor MeArg actually reduces renal function. T hese results underline the regulatory role of the L-arginine/NO pathwa y for renal function not only under basal conditions but also in ARF.