VASCULOPROTECTIVE AND CARDIOPROTECTIVE MECHANISMS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION - THE HOMEOSTATIC BALANCE BETWEEN ANGIOTENSIN-II AND NITRIC-OXIDE

The ability of the vasculature to modify its geometry in accordance wi th conditions of its microenvironment-the process of vascular remodeli ng-is an important pathobiologic process common to vascular disorders such as atherosclerosis, restenosis after angioplasty, and hypertensio n. Vascular remodeling characterizes the natural history of atheroscle rosis, contributes to increased vascular resistance, and may contribut e to the clinical complications of hypertension. A growing body of evi dence indicates that locally generated vasoactive substances such as a ngiotensin II and nitric oxide are important determinants of the natur al history of vascular disease. In particular, angiotensin II may prom ote vascular lesion formation by increasing vascular cell population v ia increased cell growth and decreased programmed cell death, and it m ay also alter extracellular matrix composition. Thus, angiotensin II i s a pleiotropic local mediator capable of modulating cell growth, prog rammed cell death, migration of vascular smooth muscle cells, and extr acellular matrix modulation, all of which are biologic mechanisms of v ascular remodeling and intimal formation. This is proposed to occur vi a a local tissue angiotensin system. Angiotensin II may also promote c hronic hypertension by modulating the vascular redox state and promoti ng the catabolism of the endothelium-derived nitric oxide, an endogeno us inhibitory vasodilator. Because angiotensin-converting enzyme (ACE) is strategically positioned to influence the activity of at least thr ee local vasoactive systems-angiotensin II, nitric oxide, and bradykin in-blocking ACE with ACE inhibition may have profound effects on ventr icular and vascular structure and function, and have particular effica cy in preventing the morbidity and mortality of vascular diseases such as hypertension and atherosclerosis.