Aldosterone receptor antagonists: biology and novel therapeutic applications.
A dysregulation of the aldosterone system has been involved in the pathophysiology of cardiovascular diseases, including myocardial failure and, partially, essential hypertension. In humans and in rat models, aldosterone action induces heart remodeling and interstitial and perivascular myocardial fibrosis. Therefore, a rationale for using aldosterone antagonists (ARAs) of the spironolactone family, which have been available for decades for the treatment of aldosterone excess syndromes, has now emerged. The development of compounds such as eplerenone, with a greater selectivity for mineralocorticoid receptors, is promising also in terms of reduction of endocrine side effects. The use of ARAs for the treatment of myocardial failure and selected cases of hypertension, in combination with the current therapy, has been strongly supported by trials such as the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). Thus, the addition of ARAs to the conventional therapy appears beneficial, leading to an improved survival rate and a reduced incidence of cardiac complications.
Magni
Paolo
P
Istituto di Endocrinologia, University of Milan, via G. Balzaretti, 9, 20133 Milano, Italy. paolo.magni@unimi.it
Motta
Marcella
M
D000450:Aldosterone / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone