ABSTRACT
Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-aldosterone system in the expression and modulation of cardiovascular disease. In contrast to the original hypothesis, the benefits of angiotensin antagonism do not emanate from the antihypertensive effect alone. Subsequent extensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacologic alteration of endothelial cell function and the ensuing changes in the biology of the vasculature. The more recent availability of direct antagonists of the AT(1) angiotensin receptor has introduced an element of doubt into this realm of clinical decision making. The receptor antagonists and the more widely studied converting-enzyme inhibitors share many endpoint attributes. Nevertheless, the partially 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 expression of cardiovascular disease. The current review will attempt to contrast the biology of angiotensin converting-enzyme inhibition with angiotensin II receptor antagonism. A discussion of the differential effects of these drug classes on endothelial cell function and on the modulation of vascular disease will be utilized to provide a theoretic framework for clinical decision making and therapeutics.
Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensinogen/metabolism , Cardiovascular Diseases/drug therapy , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Clinical Trials as Topic , Endothelium, Vascular/drug effects , Humans , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiologyABSTRACT
Clinical and basic science research has repeatedly confirmed the importance of the renin-angiotensin-aldosterone system in the pathophysiology of chronic heart failure. Accordingly, blockade of this system by angiotensin-converting enzyme (ACE) inhibitors has assumed a central role in the treatment of heart failure. Recently, angiotensin II receptor blockers (ARBs) have gained prominence as a possible substitute for ACE inhibitors in therapy for heart failure. However, clinical data compiled on this use of ARBs have shown them to be useful only as alternative therapy in ACE inhibitor-intolerant patients. Continuing large-scale clinical investigations may lead to an expansion of their role in therapy for various cardiovascular diseases.
