Cardioprotection with angiotensin‐converting enzyme inhibitors: Redefined for the 1990s

Abstract

The concept of “cardioprotection” with ACE inhibitors has evolved over the last decade. In the 1980s, protective benefits of ACE inhibitors in hypertension were established, regression of left ventricular hypertrophy was demonstrated, and improved ventricular function and survival in mild‐to‐moderate and severe congestive heart failure was documented. A further “protective” role of ACE inhibitors in coronary artery disease is emerging as more attention is focused on the concept of local tissue reninangiotensin systems. Recent contributions to the literature describe significant benefits of ACE‐inhibitor therapy in acute myocardial infarction, including suppression of ventricular arrhythmias and reduction of both early and late ventricular dilation, preservation of left ventricular function, and improved survival. All of the above effects can be considered “cardioprotective.” However, as new benefits are reported in the 1990s, a broadened view of “cardiovascular protection” emerges from investigative studies in the literature. ACE inhibitors may reduce tolerance to nitrates, reduce angina in some but not all studies, and limit smooth muscle cell proliferation (and perhaps restenosis) induced by experimental balloon angioplasty. Local vascular effects may attenuate atherosclerotic changes in the arterial wall in experimental animals and may decrease the incidence of aneurysm formation in hypertensive animals. The effectiveness of ACE inhibitors in acute myocarditis, suggested by reports that captopril may reduce lesions of murine myocarditis when administered early after infection with coxsackievirus B3, requires clinical confirmation. Despite these apparently diverse “cardiovascular protective” consequences of ACE inhibitor therapy, the mechanism(s) of action of these agents remain to be elucidated. These agents affect not only the systemic renin‐angiotensin systems, but local tissue systems as well. Debate continues as to the significance of the sulfhydryl group in certain ACE inhibitors: at the present time it is not clear whether the thiol group provides a treatment benefit. Finally, stimulation of other vasodilator systems by ACE inhibitors (bradykinin, prostacyclin) may play an important role in the “cardiovascular protective” effects of these agents.

Essential Hypertension: Evaluation and Treatment

“…Following myocardial infarction, captopril, but not other non-sulfhydryl ACE inhibitors, improves contractile performance of the stunned myocardium, reduces left ventricular dilation, and improves exercise tolerance. Left ventricular end-diastolic pressure and volumes decrease while ejection fraction increases (Kloner & Przyklenk, 1993). Compared to placebo, captopril-induced beta-endorphin plasma levels appear to correlate with exercise intensity (Handa et al, 1991).…”

“…Captopril may possess vascularendothelial protective effects. In spontaneously hy-pertensive rats, captopril prevents hypercalcemia, aneurysmal dilation, and vascular wall thickening (Kloner & Przyklenk, 1993).…”