Captopril or prostaglandin E1 ameliorate adverse renal hemodynamic effects of indomethacin in uninephrectomized rats.
Nonsteroidal anti-inflammatory drugs like indomethacin and angiotensin converting enzyme inhibitors like captopril have contrasting effects on compensatory changes in glomerular filtration rate and renal blood flow following partial nephrectomy. Conjoint treatment has been little studied. Effects of 7 days of treatment with captopril, indomethacin, or captopril + indomethacin in drinking water were studied in 50% nephrectomized Sprague-Dawley rats. Urinary protein excretion, glomerular filtration rate, effective renal plasma flow (ERPF), mean arterial pressure, renal vascular resistance, and remnant kidney weight were measured. Renal clearance studies were performed using a double-isotope, single-injection method, in conscious rats infused with either saline or saline + prostaglandin E1. Indomethacin induced significant (p less than 0.05) increases in renal vascular resistance (RVR) which were attenuated by either concurrent treatment with captopril or infusion of PGE1 at the time of study. Compensatory growth of the remnant kidney appeared not to be dependent on increments in renal blood flow; captopril decreased RVR and increased ERPF but had no effect on kidney weight, while indomethacin had no effect on ERPF and augmented remnant kidney weight. It appears effects of captopril and indomethacin on intrarenal hemodynamics in the residual kidney were counteractive, and that conjoint therapy in renal disease should be approached with caution.
Fettman
M J
MJ
Comparative Nephrology Unit, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
Wilke
W L
WL
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D002216:Captopril; D000527:Alprostadil; D007213:Indomethacin