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PHARMACOLOGY AND THERAPEUTICS: Edited by Adam Whaley-Connell

Is there a new dawn for selective mineralocorticoid receptor antagonism?

Luther, James M.

Author Information

Divisions of Clinical Pharmacology and Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

Correspondence to James M. Luther, Vanderbilt University Medical Center, 2200 Pierce Avenue, 560C RRB, Nashville, TN 37232-6602, USA. Tel: +1 615 936-3420; fax: +1 615 936-2746; e-mail:[email protected]

Current Opinion in Nephrology and Hypertension23(5):p 456-461, September 2014. |DOI:10.1097/MNH.0000000000000051

Abstract

Purpose of review 

Aldosterone and the mineralocorticoid receptor contribute to resistant hypertension and cardiovascular mortality, and mineralocorticoid receptor antagonists effectively reduce these complications. Their use is limited in certain populations with a higher risk of hyperkalemia or renal dysfunction. This review will highlight recent developments in extra-renal mineralocorticoid receptor research and the development of novel mineralocorticoid receptor antagonists.

Recent findings 

Tissue-specific knockout-out models provide definitive evidence that the vascular mineralocorticoid receptor directly contributes to hypertension and vascular remodeling, independent of renal effects. Several nonsteroidal mineralocorticoid receptor antagonists are in preclinical development or early-stage clinical trials. Several nonsteroidal mineralocorticoid receptor antagonists have demonstrated preserved cardiovascular benefit with a reduced incidence of hyperkalemia in preclinical studies.

Summary 

Novel, potent nonsteroidal mineralocorticoid receptor antagonists are in development, although their effect on cardiovascular and adverse drug events requires further investigation.

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

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Current Opinion in Nephrology and Hypertension23(5):456-461, September 2014.
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