Molecular Mechanisms of Mineralocorticoid Receptor Antagonism by Eplerenone

Title: Molecular Mechanisms of Mineralocorticoid Receptor Antagonism by Eplerenone

Volume: 5 Issue: 8

Author(s): Xiao Hu, Suzhen Li, Ellen G. McMahon, Deepak S. Lala and Amy E. Rudolph

Affiliation:

Keywords: hypertension, reninangiotensin-aldosterone system, angiotensin-converting enzyme, aldosterone antagonist., antihypertensive, histone acetyltransferase, cortical collecting tubule

Abstract: Mineralocorticoid receptor (MR) antagonism has proven to effectively attenuate the pathophysiological effects of aldosterone in clinical and experimental settings of hypertension and heart failure. MR activates transcription of target genes upon aldosterone binding, and eplerenone selectively binds to MR and blocks aldosterone- mediated activation. In this review, we summarize the preclinical and clinical evidence supporting the beneficial effects of eplerenone (INSPRATM), a selective aldosterone blocker, in the treatment of hypertension and heart failure. We also review the current status in understanding the molecular mechanisms of action of the MR and its ligand. In addition, we compare the effects of eplerenone and spironolactone, a nonselective aldosterone blocker, on the transcriptional activity of MR and provide a molecular explanation for the improved side-effect profile of eplerenone compared with spironolactone.

Cite this article as:

Hu Xiao, Li Suzhen, McMahon G. Ellen, Lala S. Deepak and Rudolph E. Amy, Molecular Mechanisms of Mineralocorticoid Receptor Antagonism by Eplerenone, Mini-Reviews in Medicinal Chemistry 2005; 5 (8) . https://dx.doi.org/10.2174/1389557054553811