Formulating clinical strategies for angiotensin antagonism: A review of preclinical and clinical studies

Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-al dosterone system in the expression and modulation of cardiovascular disease . In contrast to the original hypothesis, the benefits of angiotensin antag onism do not emanate from the antihypertensive effect alone. Subsequent ext ensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacalogic alteration of endothel ial cell function and the ensuing changes in the biology of the vasculature . The more recent availability of direct antagonists of the AT, angiotensin receptor has introduced an element of doubt into this realm of clinical de cision making. The receptor antagonists and the more widely studied convert ing-enzyme inhibitors share many endpoint attributes. Nevertheless, the par tially overlapping mechanisms of action for the two classes of angiotensin antagonists confer distinct pharmacologic properties, including side effect profiles, mechanisms of action, and theoretic salutary effects upon the ex pression of cardiovascular disease. The current review will attempt to cont rast the biology of angiotensin converting-enzyme inhibition with angiotens in II receptor antagonism. A discussion of the differential effects of thes e drug classes on endothelial cell function and on the modulation of vascul ar disease will be utilized to provide a theoretic framework for clinical d ecision making and therapeutics. (C) 2001 by Excerpta Medica, Inc.