IMPROVEMENT OF CARDIAC-FUNCTION BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITION - SITES OF ACTION

Background. The discovery of new properties of angiotensin converting enzyme (ACE) inhibitors in addition to their well-known ability to low er blood pressure, such as antiproliferative actions and antiadrenergi c and vagal-stimulating effects, has contributed to the usefulness of this class of agents in the prevention and treatment of cardiovascular diseases. Methods and Results. The contribution of an activated endoc rine and/or cardiac paracrine renin-angiotensin system to the progress ion of cardiovascular diseases with the exception of renovascular hype rtension is not fully understood. In particular, the following questio ns were addressed: 1) Is the facilitation of noradrenaline release in the genesis of arrhythmias a target for ACE inhibition? 2) Is an impai red nutritional cardiac blood flow in heart failure a target for ACE i nhibition? 3) Is the intimal hyperplasia that results from coronary an gioplasty a target for ACE inhibition? 4) Is the diastolic dysfunction associated with left ventricular hypertrophy in essential hypertensio n a target for ACE inhibition? In an isolated rat heart preparation wi th ischemia-induced arrhythmias, none of the ACE inhibitors nor an ang iotensin II antagonist was able to significantly suppress the incidenc e or severity of arrhythmias. In 12 patients with New York Heart Assoc iation functional class II-IV heart failure, a fall in cardiac filling pressures after ACE inhibition was associated with an immediate rise in cardiac output and an increase in coronary blood flow of almost 30% . In 24 patients with angina at rest, a preceding percutaneous translu minal coronary angioplasty, and a second angioplasty, control angiogra ms at 6 months revealed a high degree of restenosis in both ACE inhibi tor-treated and placebo patients. Luminal narrowing amounted to 72% in the placebo group and 61% in the ACE inhibitor group. The differences between placebo and enalapril were statistically not significant. In 12 patients with essential hypertension treated with 5 mg cilazapril, left ventricular mass was reduced by 30%, which was closely related to the change in mean arterial blood pressure. The concomitant normaliza tion of the diastolic filling pattern by ACE inhibition, however, was not related to the respective changes in blood pressure. Conclusions. Promising experimental data regarding the antiproliferative effects of ACE inhibitors in preventing restenosis could not be transferred into clinical benefits for patients who underwent repeat coronary angiopla sty. Possible antiarrhythmic effects of ACE inhibitors are not likely to be caused by their suppression of noradrenaline release during myoc ardial ischemia. ACE inhibition was effective in reducing coronary res istance in patients with severe heart failure, thereby augmenting nutr itional cardiac blood flow. ACE inhibition also effectively induced a regression of left ventricular hypertrophy in essential hypertension. The associated normalization of diastolic filling pattern may represen t an important goal in the treatment of hypertension.