Effect of NG-nitro-L-arginine methyl ester on nephrotoxicity induced by gentamicin in rats.
The present experiments were designed to assess the effect of inhibiting NO synthesis on the renal failure induced in rats by treatment with high doses of gentamicin. Eighteen Wistar rats were given gentamicin 100 mg/kg body weight/day for 5 days, whereas another 18 rats were used as control. Half of the gentamicin-treated rats and half of the controls also received the specific inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), 0.05 mg/ml in the drinking water for 5 days. Arterial pressure and renal function were measured on the 5th day of the study. In the animals treated with L-NAME, arterial pressure was higher than in untreated rats, thus suggesting that the treatment was effective in inhibiting NO synthesis. Rats that received L-NAME and gentamicin, showed higher plasma creatinine levels and higher score of renal damage, as well as lower Na+ and K+ excretion and creatinine clearance than rats that received gentamicin alone. These data showing that NO inhibition aggravates gentamicin-induced renal failure, suggest that endogenously released NO plays a protective role in gentamicin nephrotoxicity.
Rivas-Cabañero
L
L
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Rodriguez-Barbero
A
A
Arévalo
M
M
López-Novoa
J M
JM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced; D019331:NG-Nitroarginine Methyl Ester; D009336:Necrosis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D005839:Gentamicins; D009569:Nitric Oxide; D001120:Arginine; D003404:Creatinine; D019331:NG-Nitroarginine Methyl Ester