Modulation of gentamicin nephrotoxicity by chronic inhibition of angiotensin-I-converting enzyme in rat.
Perindopril, a new specific and potent inhibitor of angiotensin-I-converting enzyme, was used to evaluate the possible participation of inhibition of the renin-angiotensin system in the development of aminoglycoside-induced renal failure. Kidney function, morphology and biochemistry were evaluated at regular intervals throughout the study. Perindopril was given orally to rats at a daily dose of 2 mg/kg for 15 days prior to and during 15-day gentamicin treatment given intraperitoneally at a daily dose of 50 mg/kg. Perindopril treatment alone induced no modification in renal function or structure. Gentamicin treatment alone induced typical renal lesions which were scored as moderate and a slight but significant decrease in ACE blood levels. Concurrent treatment with perindopril and gentamicin induced a greater drop in ACE blood levels than after the administration of perindopril alone and produced more marked renal impairment than after the administration of gentamicin alone. These observations suggest that the integrity of the renin-angiotensin system may play an important role in limiting kidney injury during aminoglycoside-induced nephrotoxicity.
Morin
J P
JP
INSERM U-295, Universite de Rouen, France.
Thomas
N
N
Toutain
H
H
Borghi
H
H
Fillastre
J P
JP
D000117:Acetylglucosamine / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000652:urine; D003404:Creatinine / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020913:Perindopril; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D005839:Gentamicins; D007211:Indoles; D012964:Sodium; D003404:Creatinine; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium; D000117:Acetylglucosamine; D020913:Perindopril