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 isoforms of nitric oxide synthase (NOS) and plays a major role in maintaining the high basal renal blood flow. NO also is involved in the regulation 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 intravenously as a bolus injection (25 mg/kg over 5 min) to induce ARF. 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 (300 mg/kg); group II, MeArg (30 mg/kg); group III, Arg + MeArg (300 mg/kg, 30 mg/kg resp.). The experiments were continued for further 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 groups I-III 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 further declined after MeArg (0.46 +/- 0.06) in relation to control (0.47 +/- 0.07). This negative effect could be overcome by combined administration of Arg + MeArg (0.59 +/- 0.07). One hour after the infusion period these 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-arginine/NO pathway is involved in toxic ARF of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Schramm
L
L
Medical Clinic, University of Würzburg, Germany.
Heidbreder
E
E
Lopau
K
K
Schaar
J
J
De Cicco
D
D
Götz
R
R
Heidland
A
A
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D014502:Uranyl Nitrate / Q000633:toxicity; D019323:omega-N-Methylarginine
D014502:Uranyl Nitrate; D019323:omega-N-Methylarginine; D001120:Arginine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases