Angiotensin-converting enzyme inhibitors have been extensively studied and established in the treatment of
hypertension,
heart failure, and
ventricular dysfunction. They have various cardiac and vascular protective effects, but the relevant mechanisms of action in these areas remain to be fully understood. Possible effects of converting-
enzyme inhibition related to maintenance of normal endothelial function and inhibition of
atherosclerosis should be distinguished from effects on myointimal proliferation related to
vascular injury and regression of vascular
hypertrophy from blood pressure reduction. Experimental animal studies have showed benefit from converting-
enzyme inhibition in preventing myointimal proliferation after
vascular injury in some species, but no such effect has been shown in clinical studies of restenosis following coronary angioplasty. Laboratory studies have demonstrated a protective effect of converting-
enzyme inhibition on endothelial vasomotor function. Further studies have demonstrated prevention of
atherosclerosis in hyperlipidemic rabbits and
cholesterol-fed cynomolgus monkeys. Possible mechanisms of action apart from blood pressure lowering include inhibition of
angiotensin II and other tissue
growth factors and accumulation of
kinins. These data, among others, provide sufficient rationale for clinical studies to determine whether converting-
enzyme inhibitors can reduce atherosclerotic disease and thus widen their application as cardiac and vascular
protective agents.