The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data

Angiotensin-converting enzyme (ACE) is primarily localized (> 90%) in vario us tissues and organs, most notably on the endothelium but also within pare nchyma and! inflammatory cells. Tissue ACE is now recognized as a key facto r in cardiovascular and renal diseases. Endothelial dysfunction, in respons e to a number of risk, factors or injury such as hypertension, diabetes mel litus, hypercholesteremia, and cigarette smoking, disrupts the balance of v asodilation and vasoconstriction, vascular smooth muscle cell growth, the i nflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have delet erious effects on the heart, vasculature, and the kidneys. The imbalance re sulting from increased local formation of angiotensin II and increased brad ykinin degradation favors cardiovascular disease. Indeed ACE inhibitors eff ectively reduce high blood pressure and exert cardio- and renoprotective ac tions. Recent evidence suggests that a principal target of ACE inhibitor ac tion is at the tissue sites. Pharmacokinetic properties of various ACE inhi bitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensive s (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the signi ficance of these drug differences and their impact on clinical events. (C) 2001 by Excerpta Medica, Inc.