Systemic and renal haemodynamic effects of renin or angiotensin converting enzyme inhibition in non-human primates.
The cardiovascular actions of a renin inhibitor, U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]Val-Ile-Amp), and of an angiotensin converting enzyme (ACE) inhibitor, captopril, were determined in conscious sodium-depleted cynomolgus monkeys. Cardiac output was measured with a thermodilution technique. The hypotension induced by U-71038 was associated with a significant reduction in total peripheral resistance without alteration in cardiac output or the heart rate. A similar reduction in total peripheral resistance was observed after captopril at a dose which caused hypotension equivalent to that elicited by U-71038. The latter effects were not accompanied by significant alterations in cardiac output or the heart rate. The glomerular filtration rate was measured by the plasma disappearance of 125I-sodium iothalamate. Renin or ACE inhibition adequate to cause equivalent hypotensive responses did not change the glomerular filtration rate to a significantly different degree. The systemic and renal haemodynamic profiles of U-71038 and captopril appear to be similar, suggesting that renin and ACE inhibition elicit fundamentally similar cardiovascular effects in conscious sodium-depleted cynomolgus monkeys via a decreased formation of angiotensin II (Ang II).
Pals
D T
DT
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Ludens
J H
JH
DeGraaf
G L
GL
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012964:Sodium / Q000172:deficiency; D000092502:Renin Inhibitors
D002216:Captopril; D009842:Oligopeptides; D012964:Sodium; D000092502:Renin Inhibitors; C050898:ditekiren