Nuclear Receptors as Targets in Cardiovascular Diseases

Peter Kolkhof, Lars B arfacker, Alexander Hillisch, Helmut Haning, and Stefan Schafer 

The steroid receptor family is a subclass of nuclear hormone receptors activated by steroid hormones. This nuclear hormone receptor subfamily has six members  

Nuclear Receptors as Drug Targets. Edited by Eckhard Ottow and Hilmar Weinmann Copyright 2008 WILEY-VCH Veriag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31872-8 

Antiandrogenic and progestational symptoms such as gynecomastia, impotence and menstrual irregularities related to the clinical use of spironolactone were observed already at a very early stage [7], and recognized since 1975 as characteristic adverse effects due to the unspecific interactions of spironolactone with the AR and PR [8]. 

Despite its improved selectivity, eplerenone has a relatively low affinity for MR in vitro (about 40-fold less potent compared to spironolactone [15]), and a lower potency and efficacy in a human hypertension study in comparison to spironolactone [16]. This study showed that 100 mg eplerenone given once daily or 50 mg twice daily have an efficacy of 50-75% compared to 50 mg spironolactone twice daily. This is important since the maximal approved daily dose of eplerenone for the treatment of hypertension is 100 mg in the US (eplerenone has no approval for this indication in Europe). 

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Nuclear receptors also play an important role as drug targets in cardiovascular diseases. Peter Kolkhof, Lars Barfacker, Alexander Hillisch, Helmut Haning and Stefan Schafer review the mineralocorticoid receptor, peroxisome proliferator-activated receptor / and thyroid hormone receptors in detail based upon their therapeutic value, and additionally vitamin D receptor, retinoic add receptors and retinoid X receptors as well as liver X receptors are covered with a special focus on their role in cardiovascular diseases. 

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