Aldosterone target organ protection by eplerenone
Aldosterone target organ protection by eplerenone
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DOI：
10.1016/j.mce.2003.10.047
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发表时间：
2004-03-31
影响因子：
4.1
通讯作者：
McMahon, EG
中科院分区：
文献类型：
--
作者：
Rudolph, AE;Rocha, R;McMahon, EG
醛固酮对肾内钠单向经上皮转运的典型矿化皮质效应长期以来被认为是该激素的主要作用。然而，有令人信服的证据表明，醛固酮的其他外源性作用是通过激活心脏、脉管系统和大脑中的矿物皮质激素受体（MRs）来介导的。现在假设醛固酮的许多有害影响是通过这些非经典靶器官的MR激活介导的。选择性醛固酮阻滞剂eplerenone （Inspra(TM)）正在开发中，用于治疗高血压和心肌梗死（MI）后心力衰竭。临床和临床前研究表明，醛固酮升高与高血压、左心室和血管重构、心脏、肾脏和脑血管炎症和损伤以及心力衰竭患者死亡风险增加有关。高血压和心力衰竭实验模型的多项研究表明，依普利酮选择性阻断醛固酮可有效保护心功能，部分通过减少醛固酮靶器官的血管炎症，减轻左心室不适应重构和组织血管损伤。2003爱思唯尔爱尔兰有限公司版权所有。
The classical mineralocorticoid effect of aldosterone on unidirectional transepithelial sodium transport in the kidney was long thought to be the predominant effect of this hormone. However, there is convincing evidence for additional extrarenal actions of aldosterone that are mediated via activation of mineralocorticoid receptors (MRs) in the heart, vasculature and brain. It is now postulated that many of the detrimental effects of aldosterone are mediated through MR activation in these nonclassical target organs. The selective aldosterone blocker, eplerenone (Inspra(TM)) is under development for human therapeutic use for treatment of hypertension and heart failure post-myocardial infarction (MI). Clinical and preclinical studies have linked elevated aldosterone to hypertension, left ventricular and vascular remodeling, cardiac, renal, and cerebral vascular inflammation and injury, and increased risk of mortality in heart failure patients. Multiple studies in experimental models of hypertension and heart failure demonstrate that selective blockade of aldosterone by eplerenone effectively preserves cardiac function, attenuates maladaptive left ventricular remodeling and tissue and vascular injury in part by reducing vascular inflammation in aldosterone target organs. (C) 2003 Elsevier Ireland Ltd. All rights reserved.