ACUTE HEMODYNAMIC-EFFECTS OF DRUGS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM IN ACUTE HEART-FAILURE

Objective: To determine the role of the renin-angiotensin system in a model of acute heart failure. Methods: Placebo or drugs (Ro 44-9375, a renin inhibitor; captorpril, an angiotensin-converting enzyme [ACE] i nhibitor; or DuP 532, an angiotensin II receptor[AT1]antagonist) were given to anesthetized splenectomized dogs (n = 12 for each group) for 50 mins after a volume load (dextran 70, 25 mL/kg over 10 mins) during rapid right ventricular pacing at 250 beats/min. Total vascular compl iance and capacitance were determined from mean circulatory filling pr essure-blood volume curves during transient circulatory arrests induce d by acetylcholine. Cardiac index was measured by thermal dilution. Re sults: Compared with the untreated group, all three drugs significantl y reduced systemic pressure and total peripheral resistance while incr easing arterial compliance. Captopril alone increased cardiac index (2 5+/-11 versus -23+/-13 mL/kg/min) and reduced pulmonary capillary wedg e pressure (16.6+/-0.7 versus 21.9+/-1.0 mmHg). None of the drugs alte red the mean circulatory filling pressure, total vascular compliance o r capacitance, stressed or unstressed blood volumes, or central blood volume. Conclusion: The renin-angiotensin system is not strongly impli cated in the hemodynamic manifestations of this model of acute heart f ailure. These drugs had effects on the arterial but not the venous sid e of the circulation. Captopril alone reduced pulmonary capillary wedg e pressure, perhaps by nonangiotensin effects.