The renin-angiotensin system in aminoglycoside-induced acute renal failure.
To examine the role of the renin-angiotensin system in aminoglycoside-induced acute renal failure, we gave rats gentamicin (80 mg/kg/day), gentamicin + captopril (an angiotensin-converting enzyme inhibitor), captopril alone or saline sham injections, for 10 days. Blood pressure, sodium excretion, urine osmolality and creatinine clearance were measured four times during treatment. Plasma renin activity, angiotensin I-converting enzyme and renal histology were determined at sacrifice. Although angiotensin I-converting enzyme activity was markedly suppressed by captopril treatment, the addition of captopril failed to consistently influence blood pressure or urine osmolality. In addition, it did not promote natriuresis in the face of gentamicin toxicity. Creatinine clearance decreased progressively in groups receiving gentamicin and was lowest (P less than .05) in the groups receiving gentamicin + captopril. Captopril did not prevent the development of tubular epithelial nor glomerular endothelial changes associated with gentamicin toxicity. In a separate experiment rats received captopril for 3 days prior, before receiving the gentamicin + captopril regimen for 10 days. Captopril pretreatment did not influence the results. This study does not support a pivotal role for the renin-angiotensin system in the production of the decreased glomerular filtration rate observed in nephrotoxic acute renal failure induced by gentamicin in rats.
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D005839:Gentamicins; D011392:Proline; D002216:Captopril