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

• Published in: Cardiovascular research 1997-06, Vol.34 (3), p.464-472
• Main Authors: SHANNON, R. P, FRIEDRICH, S, MATHIER, M, KNIGHT, D. R
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; beta-Cyclodextrins; Biological and medical sciences; Blood Pressure - drug effects; Captopril - pharmacology; Cardiac Pacing, Artificial; Cardiovascular system; Cyclodextrins - pharmacology; Dipeptides; Dogs; Dose-Response Relationship, Drug; Female; Heart Failure - blood; Heart Failure - physiopathology; Male; Medical sciences; Morpholines; Pharmacology. Drug treatments; Regional Blood Flow - drug effects; Renal Circulation - drug effects; Renin - antagonists & inhibitors; Renin - blood; Vasodilator agents. Cerebral vasodilators
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(97)00066-7

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). 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. 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). 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.