Effects of renin inhibition compared to angiotensin converting enzyme inhibition in conscious dogs with pacing-induced heart failure.
OBJECTIVE
To compare the effects of angiotensin converting enzyme inhibition (ACEI) (captopril 1 mg/kg i.v.) to direct renin inhibition (CP80794 3 mg/kg i.v.) on left ventricular and systemic hemodynamics and peripheral blood flows in advanced congestive heart failure (CHF).


METHODS
Conscious chronically instrumented dogs (n = 14) were treated with captopril, 1 mg/kg, i.v., or CP80794, 3 mg/kg, i.v., before and after development of advanced CHF induced by 4-7 weeks of rapid ventricular pacing. After advanced CHF, comparisons between the inhibitors were made at equihypotensive doses.


RESULTS
In advanced CHF, both agents caused comparable reductions in mean arterial pressure (MAP) (-22% from 79 +/- 4 mmHg) and comparable increases (P < 0.01) in cardiac output (CP80794, 1.4 +/- 0.3 to 1.8 +/- 0.1 l/min; captopril, 1.4 +/- 0.1 to 1.9 +/- 0.1 l/min). Neither agent had a significant effect on LV contractility. In contrast, CP80794 caused a greater (P < 0.05) increase in renal blood flow (66 +/- 6% from 64 +/- 5 ml/min) compared to captopril (33 +/- 4% from 66 +/- 7 ml/min).


CONCLUSIONS
Renin inhibition with CP80794 and ACEI with captopril caused comparable hemodynamic effects in advanced CHF. However, CP80794 caused significantly greater increases in renal blood flow and suppressed renin activity to a greater degree than captopril.
Shannon
R P
RP
Cardiovascular Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA, USA.
Friedrich
S
S
Mathier
M
M
Knight
D R
DR
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D003505:Cyclodextrins / Q000494:pharmacology*; D004151:Dipeptides; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009025:Morpholines; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D047392:beta-Cyclodextrins; D000092502:Renin Inhibitors
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D003505:Cyclodextrins; D004151:Dipeptides; D009025:Morpholines; D012083:Renin; D047392:beta-Cyclodextrins; D000092502:Renin Inhibitors; C076964:terlakiren