787-1 ACE Inhibition Acutely Stimulates Sympathetic Tone and Improves Myocardial Contractility and Coronary Flow in Coronary Artery Disease. A Bradykinin-related Effect?

The acute effects of ACE inhibition on neurohormonal activation are complex. Sympathetic tone decreases as a direct result of angiotensin II reduction; however, an increase in bradykinin may stimulate sympathetic tone. Consequently, divergent coronary and systemic hemodynamic effects may ensue. As these acute ACE inhibitor effects are incompletely identified in humans, 49 pts with significant (>70%) CAD received enalaprilat, perindoprilat or captopril intravenously, which resulted in immediate (≤5’) 73% ACE inhibition and a 52% reduction in arterial angiotensin II. Twenty-two patients received placebo. During a 15-minute study protocol, placebo induced no changes. In the treated group, arterial norepinephrine (NE) increased at 5 and 15 minutes by 11% and 12%, respectively, and arterial epinephrine (E) by 11% and 14%, respectively. Heart rate did not change, but contractility (VMAX) increased by 13% and 4%, respectively. Mean arterial pressure (MAP) decreased by 2% and 5% and systemic vascular resistance (SVR) decreased by 4% and 7%, respectively. Despite the reduction in coronary perfusion pressure, coronary blood flow (CBFj increased by 8% at 5 minutes, while coronary vascular resistance ICVR) decreased by 10% and 11%, respectively, at 5 and 15 minutes. Arterial 6-keto-F2α, the prostacyclin metabolite, was 52% higher compared to placebo, but increased late, at 15 minutes. Other prostaglandins and cardiac neurohormonal balances remained unaltered. Thus, in contrast to the well-known modulation of sympathetic activity by chronic converting enzyme inhibition, acute ACE inhibition results in an immediate increase in circulating catecholamines and improves myocardial contractility and coronary flow. The effect on sympathetic tone and contractility cannot be explained by changes in circulating angiotensin II and prostaglandins or cardiac renin-angiotensin, which suggests a bradykinin-related effect