Cardiovascular benefits of aldosterone receptor antagonists.
There is considerable evidence in the setting of cardiovascular disease to suggest that, in addition to the classic effects of aldosterone on sodium retention, blood volume, blood pressure and potassium homeostasis, aldosterone is involved in fibrotic end-organ damage by means of intermediate mechanisms involving an interplay between the mineralocorticoid receptor, sodium intake and a variety of molecular messengers. Such processes may help to explain the reduction in mortality that can be achieved in patients with severe heart failure and post-myocardial infarction by the addition of an aldosterone receptor antagonist to standard therapy. Studies in animal models treated with the nitric oxide inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), angiotensin II and salt, with and without adrenalectomy, have demonstrated that myocardial damage can be eliminated by adrenalectomy or by administering an aldosterone receptor antagonist and is induced by adding back aldosterone to adrenalectomized animals. Importantly, at least a modest salt intake is an obligate co-factor. Other animal studies have established that an early stage in aldosterone-associated myocardial damage involves the release of proinflammatory molecules, including cyclo-oxygenase type 2, osteopontin and monocyte chemoattractant protein-1. Taken together, these findings suggest that aldosterone in the presence of salt intake is a major cardiovascular risk factor mediated by inflammatory and fibrotic processes. Thus, mineralocorticoid receptor antagonists are likely to be effective additional agents to treat a broad range of cardiovascular diseases.
Williams
G H
GH
Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts 02215-5817, USA.
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects*; D005260:Female; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D023421:Models, Animal; D016032:Randomized Controlled Trials as Topic
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone