title: Effect of nitric oxide synthesis modification on renal function in gentamicin-induced nephrotoxicity.
abstract: We evaluated the effect of acute or chronic nitric oxide (NO) synthesis activation or inhibition in rats with gentamicin-induced acute renal failure. Rats received gentamicin 100 mg/kg per day for 6 days, or isotonic saline. Some animals of each group also received N(G)-monomethyl-l-arginine (l-NAME, 4 mg/kg per day) or l-arginine (1%) in the drinking water for 6 days (chronic NO synthesis modification). In another experimental set, animals were treated with gentamicin or saline for 6 days and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured before and after the infusion of l-NAME (50 mg/h per kg) or l-arginine (60 mg/h per kg) (acute NO synthesis modification). Acute l-NAME administration induced a decrease in GFR and RPF both in control and gentamicin treated animals. Chronic l-NAME treatment induced an impairment in GFR only in gentamicin-treated animals. Acute l-arginine administration did not modify renal function in any experimental group whereas chronic l-arginine administration improved renal function only in gentamicin-treated animals. Urinary excretion of N-acetyl-β-d-glucosaminidase and alkaline phosphatase was increased by chronic treatment with l-NAME in both groups, whereas l-arginine had no effect. In conclusion, NO synthesis inhibition aggravates gentamicin-induced renal damage. However, chronic NO synthesis stimulation partially prevents against gentamicin nephrotoxicity, thus suggesting that increased renal NO synthesis during gentamicin-induced nephrotoxicity plays a protector role on renal function.
authors.affiliation: Instituto Reina Sofı́a de Investigación Nefrológica, Departamento de Fisiologı́a y Farmacologı́a, Facultad de Medicina, Universidad de Salamanca, Avenida Campo Charro s/n, 37 007 Salamanca, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Valdivielso
authors.forename: L
authors.initials: L
authors.lastname: Rivas-Cabañero
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Barriocanal
authors.forename: J M
authors.initials: JM
authors.lastname: López-Novoa