Hu Xiao, Li Suzhen, McMahon Ellen G, Lala Deepak S, Rudolph Amy E
Department of Genomics and Biotechnology, Pfizer Inc., St. Louis, MO 63017, USA.
Mini Rev Med Chem. 2005 Aug;5(8):709-18. doi: 10.2174/1389557054553811.
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.
在高血压和心力衰竭的临床及实验环境中，盐皮质激素受体（MR）拮抗作用已被证明能有效减轻醛固酮的病理生理效应。醛固酮结合后，MR会激活靶基因的转录，而依普利酮会选择性地与MR结合，并阻断醛固酮介导的激活作用。在本综述中，我们总结了支持选择性醛固酮阻断剂依普利酮（Inspra）治疗高血压和心力衰竭有益作用的临床前和临床证据。我们还回顾了目前在理解MR及其配体作用分子机制方面的现状。此外，我们比较了依普利酮和非选择性醛固酮阻断剂螺内酯对MR转录活性的影响，并对依普利酮与螺内酯相比副作用改善的情况提供了分子解释。
