Mineralocorticoid receptor and cardiac arrhythmia.

Abstract

Mineralocorticoid receptor (MR) activation has been shown to play a deleterious role in the development of heart disease in studies using specific MR antagonists (spironolactone, eplerenone) in both experimental models and patients. Pharmacological MR blockade attenuates the transition to heart failure (HF) in models of systolic left ventricular dysfunction and myocardial infarction, as well as diastolic dysfunction, in rats and mice. In humans, MR antagonism is highly beneficial in patients with mild or advanced HF and postinfarct HF. The consequences of aldosterone and MR activation for cardiac arrhythmia and its prevention and/or correction by MR antagonists are often underestimated.  Activation of MR modulates cardiac electrical activity, causing atrial and ventricular arrhythmias. A pro-arrhythmogenic effect of aldosterone (possibly partly dependent on fibrosis) has been suggested by several studies. Cardiac MR activation has important consequences for the control of cellular calcium homeostasis, action potential lengthening, modulation of calcium transients and sarcoplasmic reticulum diastolic leaks, resulting in the promotion of rhythm disorders. Aldosterone and/or MR activation (in both cardiomyocytes and coronary vessels) result in vascular dysfunction and also contribute to pro-arrhythmogenic conditions.  Together, the pro-arrhythmic effects of aldosterone and/or MR may explain the highly beneficial effect of MR antagonism, namely a decrease in the incidence of sudden death, observed in the Randomized Aldactone Evaluation Study (RALES) and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) studies.

• Authors: Basile Gravez, Antoine Tarjus, Frederic Jaisser
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 40 Issue 12 Pg. 910-5 (Dec 2013) ISSN: 1440-1681 [Electronic] Australia
• PMID: 23888997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2013 Wiley Publishing Asia Pty Ltd.

Chemical References

• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Aldosterone

Topics

• Aldosterone (metabolism)
• Animals
• Arrhythmias, Cardiac (complications, drug therapy, metabolism, pathology)
• Atrial Fibrillation (etiology, pathology, prevention & control)
• Death, Sudden, Cardiac (etiology, pathology, prevention & control)
• Fibrosis
• Humans
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Randomized Controlled Trials as Topic
• Receptors, Mineralocorticoid (metabolism)