Angiotensin-converting enzyme inhibition to enhance vascular health—clinical and research models

Protection of the endothelium, the metabolically active inner lining of the vasculature, appears to be a key factor in maintaining cardiovascular (CV) health. The endothelium responds to hemodynamic and hormonal factors by secreting substances that maintain vascular homeostasis. Damage to the endothelium is an initial step in the development of CV disease. Angiotensin-converting enzyme (ACE) inhibitors, which block the formation of the vasoconstricting substance, angiotensin II, have proved to be a key therapy for hypertension and congestive heart failure. The activity of these agents in enhancing vascular health appears to be a critical factor in their therapeutic effectiveness. Large-scale clinical trials over the past decade have shown that ACE inhibition is an effective therapeutic means of not only prolonging survival and reducing morbidity after acute myocardial infarction, but also reducing all-cause mortality and morbidity in patients at high risk for CV disease, including patients with diabetes. ACE is found in far greater amounts in tissue than in plasma. Studies indicate that ACE inhibitors act at the tissue level to provide long-term cardioprotective effects that include a reduction in the progression of atherosclerosis. An issue to resolve is how much ACE inhibition is needed at the tissue level to reverse or prevent further vascular damage.