title: Nitrendipine protects against aminoglycoside nephrotoxicity in the rat.
abstract: Aminoglycoside nephrotoxicity is a common clinical problem among hospitalized patients despite close attention to pharmacokinetics and dosing schedules. The present study was designed to evaluate the potential protective effect of nitrendipine, a calcium channel blocker, on the natural history of gentamicin renal injury in the rat. Gentamicin was administered intramuscularly in a dose of 40 mg/kg/day for 12 days to adult Fischer rats. Nitrendipine was given by gavage on a b.i.d. schedule in a dose of 30 mg/kg/day or 10 mg/kg/day. Gentamicin alone caused a significant decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF). Concurrent administration of nitrendipine did not influence RPF, but promoted a significant increase in GFR. Nitrendipine also prevented the increase in urinary excretion of N-acetyl-glucosaminidase and beta-glucosidase, enzymatic markers of renal tubular injury in the gentamicin-treated animals. Gentamicin-induced pathologic injury was significantly ameliorated by nitrendipine. Renal cortical gentamicin content was diminished, but not significantly, by nitrendipine. The exact mechanism of action of nitrendipine in aminoglycoside-induced renal injury remains unknown. These observations suggest a potential pharmacologic approach to preventing a common problem with substantial morbidity.
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000617:Aminoglycosides / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D005839:Gentamicins / Q000633:toxicity; D007672:Kidney Cortex / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D009568:Nitrendipine / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009568:Nitrendipine; D000118:Acetylglucosaminidase