Angiotensin-converting enzyme inhibition: prospects for the future.

Abstract

Angiotensin-converting enzyme (ACE) is a widely distributed dipeptidyl carboxydipeptidase. Using computer analysis of the binding of radiolabeled ACE inhibitors, we have mapped the distribution of ACE in normal animals and in models of disease, and have studied the tissue effects of ACE inhibitors. In the myocardium, ACE is located in vascular and valvular structures as well as in the atria and ventricles. Its concentration is increased in myocardial hypertrophy in the infarct model of heart failure. Chronic ACE-inhibitor therapy prevents myocardial hypertrophy. In the brain, ACE is localized in multiple specific sites where its role is unknown. Following oral ACE-inhibitor treatment, effects are restricted predominantly to areas devoid of blood-brain barrier. Early studies suggest ACE inhibitors enhance cognition. In the testis, ACE is located in the seminiferous tubules where its function is unknown. It is not inhibited following oral ACE-inhibitor treatment. In the kidney and gastrointestinal tract, ACE is in high concentration in the epithelial brush border where its function is unknown. In clinical use ACE inhibitors primarily affect the cardiovascular system. With pharmacological developments, ACE inhibitors targeted for specific organs may have effects predominantly in the brain, heart, reproductive system, or gastrointestinal tract.