title: Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone.
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 (INSPRA), 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.
authors.affiliation: Department of Genomics and Biotechnology, Pfizer Inc., St. Louis, MO 63017, USA. Xiao.Hu@pfizer.com
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Suzhen
authors.initials: S
authors.lastname: Li
authors.forename: Ellen G
authors.initials: EG
authors.lastname: McMahon
authors.forename: Deepak S
authors.initials: DS
authors.lastname: Lala
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rudolph
mesh_terms: D000450:Aldosterone / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D008024:Ligands; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D018161:Receptors, Mineralocorticoid / Q000187:drug effects*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: D008024:Ligands; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone