Azotemia during chronic converting enzyme inhibition with enalapril in sodium-depleted rats: role of renal circulatory changes.
Chronic administration of the angiotensin-converting enzyme inhibitor enalapril to sodium-restricted rats causes azotemia and elevations in serum creatinine. This study was undertaken to determine the contribution of altered systemic and renal hemodynamics to the reductions in renal function in sodium-restricted rats treated with enalapril. Animals were maintained for 21 days on a sodium-restricted diet (0.04 +/- 0.01 mEq Na+/24 h). Enalapril was administered in the drinking water (300 mg/L) to half the rats. Regional blood flows were measured in animals anesthetized with pentobarbital (50 mg/kg, i.p.) using the radioactive microsphere technique. Converting enzyme inhibition (CEI) reduced mean arterial pressure (130.8 +/- 5.9 vs 60.3 +/- 6.1 mm Hg, p less than 0.001), and increased cardiac index (346 +/- 33 vs. 437 +/- 28 ml/min/kg, p less than 0.05). Total peripheral resistance was significantly lower in enalapril-treated rats [0.406 +/- 0.049 vs. 0.166 +/- 0.013 arbitrary resistance units (RU), p less than 0.001]. Renal blood flow was maintained (control, 2.93 +/- 0.21 vs. enalapril, 2.55 +/- 0.28 ml/min/100 g, p = NS) despite a 54% decrease in perfusion pressure due to decreased renal vascular resistance (42.6 +/- 1.7 vs. 25.2 +/- 2.9 RU, p less than 0.001). CEI reduced coronary blood flow (2.76 +/- 0.22 vs. 1.59 +/- 0.19 ml/min/100 g, p less than 0.001), but did not change coronary vascular resistance (50.2 +/- 4.6 vs. 44.0 +/- 4.3 RU, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003326:Coronary Circulation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D004656:Enalapril; D003404:Creatinine; D007213:Indomethacin