Role of L-arginine-derived NO in ischemic acute renal failure in the rat.
Nitric oxide (NO) is involved in the regulation of renal perfusion and glomerular hemodynamics under basal conditions. We examined the hypothesis that L-arginine-derived NO modifies ischemic acute renal failure (ARF) in the rat. After a basal period ischemia was induced by clamping of both renal arteries (40 min). Thereafter, in the reperfusion period, we intravenously infused L-arginine (Arg, 300 mg/kg/60 min), or L-monomethylarginine (MeArg, 30 mg/kg/60 min), or Arg + MeArg (300 mg/kg/60 min, 30 mg/kg/60 min, resp.). Besides monitoring of urinary flow rate and arterial blood pressure, and determination of sodium excretion, glomerular filtration rate (GFR, mL/min/100 g) was estimated at the end of the infusion period and again after another 30 and 120 min by inulin clearance (fluorescence-marked inulin). In the basal period GFR showed no differences between the groups (Arg: 0.86 +/- 0.07, MeArg: 0.92 +/- 0.06, Arg + MeArg: 0.89 +/- 0.08, control: 0.84 +/- 0.07). At 180 min after the beginning of the reperfusion period, GFR was 0.13-0.02 in the control group. After administration of Arg, a remarkable and persistent increase in GFR was observed (0.28 +/- 0.03), whereas infusion of MeArg showed no significant effects (0.13 +/- 0.04). Combined administration of Arg + MeArg revealed a moderate increase of GFR (0.19 +/- 0.05), ranging between the Arg and the control group. Also, 60 and 90 min after the beginning of the reperfusion period, the highest values for GFR were obtained in the Arg group. We conclude that in this model of ischemic ARF in the rat, L-arginine-derived NO is capable of improving renal function. These data underline the regulatory role of the L-Arg-NO pathway for renal function, not only under normal conditions, but also in ARF.
Schramm
L
L
Department of Nephrology, University of Würzburg, Germany.
Heidbreder
E
E
Schmitt
A
A
Kartenbender
K
K
Zimmermann
J
J
Ling
H
H
Heidland
A
A
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D014563:Urodynamics / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases