Mineralocorticoid Receptor, the Main Player in Aldosterone-Induced Large Artery Stiffness

Abstract

See related article, p 520–526 Aldosterone, a key hormone in the control of sodium and potassium balance, regulates extracellular volume and blood pressure. In the kidney, aldosterone, released by adrenal glomerulosa in response to angiotensin II, high potassium levels, and adrenocorticotropic hormone, classically acts through the mineralocorticoid receptor (MR), a ligand-activated transcription factor. The extensive expression of the MR in the cardiovascular system, including in the heart, endothelial cells, vascular smooth muscle cells, and mesangial cells, provides supportive evidence for a role of aldosterone in renal and cardiovascular injuries. Excess mineralocorticoid, in the context of inappropriate salt status, is a mediator of cardiac fibrosis, left ventricular hypertrophy, and hypertension, in a blood pressure–independent manner.1 The role of aldosterone in cardiovascular remodeling is emphasized in patients with primary hyperaldosteronism type 1 (also called glucocorticoid remediable hyperaldosteronism) where cardiac and vascular damages precede the development of hypertension.2 MR blockers have been shown to prevent vascular fibrosis, hypertrophic remodeling, inflammation, and impaired vascular reactivity in a blood pressure–independent manner in animal models of hypertension1 and vascular fibrosis in hypertensive patients stage 1.3 The demonstration of the benefits of MR blockade in chronic heart failure and hypertension emphasizes the importance of MR signaling pathways in cardiac and hypertensive diseases. Indeed, in patients with severe chronic heart failure, in addition to standard care, which included angiotensin-converting enzyme blockers or angiotensin II receptor blockers, spironolactone has been associated with a 30% improvement in survival (RALES [Randomized ALdactone Evaluation Study]).1 Similar observation has been made with eplerenone added to standard care in heart failure after myocardial infarction (EPHESUS [Eplerenone post-Acute Myocardial Infarction heart failure Efficacy and Survival …