Intrarenal converting enzyme inhibition in rabbit.
The role of the intrarenal renin-angiotensin system on the control of renal blood flow in the rabbit was pursued in this investigation. Blood pressure (BP) and renal blood flow (RBF) were monitored in New Zealand white rabbits anesthetized with pentobarbital. Control RBF and changes in RBF elicited by infusions of angiotensin I (AI) were determined by electromagnetic flowmetry. In Group 1 (n = 7), BP and RBF responses to AI infused i.a. and i.v. were evoked in the control period and the effects of a low i.a. dose of captopril to inhibit selectively renal angiotensin converting enzyme (ACE) and then a high i.a. dose to inhibit maximally renal ACE were determined. Low dose captopril depressed the RBF response to i.a. AI by 67% without an effect on the response to i.v. AI. RBF was increased by 15.0% and renal vascular resistance (RVR) was decreased by 14.4% by low dose captopril. High dose captopril had no further effect on the response to i.a. AI, but decreased the RBF response to i.v. AI by 72%. RBF and RVR were further changed by high dose captopril. In Groups 2 and 3, high dose captopril was administered after either indomethacin or saline vehicle. Captopril increased RBF, decreased RVR, and blocked responses to AI similarly whether prostaglandin synthesis was inhibited or not. The results indicate that renal vasodilation in the rabbit can be produced by selective renal ACE inhibition with a low dose of captopril, but that systemic ACE inhibition also contributes to this effect when a high dose is given.
Li
T
T
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Zimmerman
B G
BG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D002216:Captopril; D007213:Indomethacin