Comparison of the effect of renin inhibition and angiotensin-converting enzyme inhibition in ovine heart failure.
The acute hemodynamic and hormonal effects of incremental doses of a specific ovine renin inhibitor (RI: EMD 52 297) and captopril were compared in an ovine model of heart failure. Both RI and captopril inhibited the renin-angiotensin II (ANG II) system, although the decrease in plasma aldosterone (ALDO) was significant only during captopril infusion. Both agents exhibited strong vasodilator properties with similar decreases in mean arterial pressure (MAP, maximum decrease: RI = -20.5 +/- 2.2 mm Hg, p less than 0.001; captopril = -19.8 +/- 1.7 mm Hg, p less than 0.001) and left atrial pressure (LAP, maximum, decrease: RI = -6.8 +/- 1.5 mm Hg, p less than 0.01; captopril = -6.9 +/- 0.4 mm Hg, p less than 0.01) along with a slight increase in cardiac output (CO, maximum increase: RI = 0.54 +/- 0.11 L/min; captopril = 0.79 +/- 0.26 L/min). The slope of the response between MAP and LAP was similar in all animals, indicating that the agents have a similar effect on cardiac preload and afterload. The similar hemodynamic actions of RI and captopril in this model of congestive heart failure suggest that beneficial effects are due to inhibition of ANG II. Thus, orally active renin inhibitors may offer a useful therapeutic alternative when side effects preclude use of angiotensin-converting enzyme (ACE) inhibitors.
Fitzpatrick
M A
MA
Department of Cardiology, Princess Margaret Hospital, Christchurch, New Zealand.
Rademaker
M T
MT
Charles
C J
CJ
Yandle
T G
TG
Espiner
E A
EA
Ikram
H
H
Nussberger
J
J
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D002404:Catheterization; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D000092502:Renin Inhibitors
D000450:Aldosterone; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D009320:Atrial Natriuretic Factor; D002216:Captopril; D009842:Oligopeptides; D000092502:Renin Inhibitors; C064739:EMD 52297