Aldosterone and the mineralocorticoid receptor

Abstract

For decades, the role of aldosterone was thought to be limited to salt and water homeostasis control. This traditional view of the action of aldosterone restricted to sodium reabsorption in epithelial tissues must be revisited. Clinical trials have demonstrated the therapeutic benefit of MR blockade in heart failure of various origins. The beneficial effects of MR inhibition in patients with heart diseases emphasize the importance of this receptor in cardiovascular tissue. Significant progress have been made in understanding the pathological situations in which MR blockade is beneficial as well as the mechanisms underlying the deleterious effects of MR activation. Experimental studies indicated that chronic activation of the MR in target tissues induces structural and functional changes in the heart, kidneys and blood vessels. These deleterious effects include cardiac and renal fibrosis, inflammation and vascular remodeling. Aldosterone is generally considered as the main ligand of MR. However, MRs bind mineralocorticoids and glucocorticoids with equal affinity. Since the selectivity enzyme 11 beta hydroxysteroid dehydrogenase type II (11 beta HSD2) is not active in cardiomyocytes, the question of which ligand activates MR in these cells is thus the subject of intense debate. The interaction of MR activation with other important players in cardiac pathophysiology, such as salt, oxidative stress, and Ang II, suggests that the combined use of MR antagonists and other drugs may have synergic beneficial effects. Experimental data also suggest that MR antagonists could have wider use than they do today and perhaps extended to various systemic diseases that affect cardiac function.