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Cardiovascular Research 1997 34(3):464-472; doi:10.1016/S0008-6363(97)00066-7
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

Effects of renin inhibition compared to angiotensin converting enzyme inhibition in conscious dogs with pacing-induced heart failure

Richard P. Shannon*, Steven Friedrich, Michael Mathier and Delvin R. Knight

Cardiovascular Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA, USA
Department of Cardiovascular Diseases, Pfizer Central Research, Groton CT, USA

* Corresponding author. Cardiovascular Division, West Roxbury VA Medical Center, 1400 VFW Parkway, West Roxbury, MA 02132, USA. Tel.: +1 (617) 323-7700, ext. 6838; fax: +1 (617) 363-5550.

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.

KEYWORDS Renin inhibition; ACE inhibitors; Heart failure; Blood flow, peripheral; Hemodynamics; Dog, anesthetized


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