These observations demonstrate that significant sources of tissue ACE in human atherosclerotic plaques are regions of inflammatory cells, especially areas of clustered macrophages as well as microvessel endothelial cells. These results suggest that ACE accumulation within the plaque may contribute to an increased production of local angiotensin that may participate in the pathobiology of coronary artery disease. Plaque ACE probably is an important target of drug action.

ET-1 induces a strong and sustained pressor response in vessels 1 and systemic hypertension in the rat.2 It also stimulates mitogenesis in vascular smooth muscle cells.3 These studies suggest the potential importance of endothelin in the pathophysiology of hypertension 2 -4 and atherosclerosis.3 Angiotensin I converting enzyme (ACE) inhibitors generally have been used as antihypertensive drugs. However, the precise mechanism of the antihypertensive effects of ACE inhibitors has not been fully elucidated. In addition, there is recent evidence for new important functions of ACE inhibitors in the cardiovascular field. ACE inhibitors can induce regression of intimal hyperplasia, whereas other antihypertensive drugs are ineffective in this regard.5 Clinical trials in patients with chronic congestive heart failure demonstrated a significant reduction in mortality with ACE inhibitor therapy. 6 Although ACE inhibition diminishes the formation of a pressor peptide, angiotensin II, 7 it also diminishes degradation of kinins, which are vasodepressor peptides.8 Bradykinin stimulates the synthesis of prostaglandin I 2 and endothelium-derived relaxing factor, 9 recently identified as nitric oxide (NO). 910 NO not only antagonizes the effects of ET-1 of vasoconstriction 11 and mitogenesis of

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