McManus Frances, McInnes Gordon T, Connell John M C
University of Glasgow, Glasgow, UK.
Nat Clin Pract Endocrinol Metab. 2008 Jan;4(1):44-52. doi: 10.1038/ncpendmet0676.
Increasing recognition of the role of aldosterone in cardiovascular disease has been supported by a significant body of evidence from animal models. This evidence has been translated into clinical practice, and large-scale, randomized, placebo-controlled trials have confirmed the beneficial effects of mineralocorticoid blockade in patients with heart failure. As a consequence, there has been a resurgence in the use of mineralocorticoid-receptor antagonists in clinical practice that has prompted the search for a potent and specific antagonist without the sexual side effects of spironolactone. Eplerenone, a mineralocorticoid-receptor antagonist with minimal binding to the progesterone and androgen receptors, is now licensed for treatment of heart failure in Europe and heart failure and hypertension in the US; it has also been proposed as a treatment for a variety of cardiovascular conditions. This article reviews the current concepts of the actions of aldosterone at a cellular level. Recent findings regarding its role as a cardiovascular hormone, both in animal models and human studies, are discussed. We also describe the development of mineralocorticoid-receptor blockers following the isolation of aldosterone and discuss the subsequent search for a specific mineralocorticoid antagonist. In addition we detail the effects of eplerenone in a number of clinical situations and outline its potential future applications.
动物模型的大量证据支持了人们对醛固酮在心血管疾病中作用的认识不断增加。这些证据已转化为临床实践，大规模、随机、安慰剂对照试验证实了盐皮质激素阻断对心力衰竭患者的有益作用。因此，临床实践中盐皮质激素受体拮抗剂的使用有所复苏，这促使人们寻找一种强效且特异性的拮抗剂，而没有螺内酯的性副作用。依普利酮是一种与孕酮和雄激素受体结合最少的盐皮质激素受体拮抗剂，目前在欧洲被批准用于治疗心力衰竭，在美国被批准用于治疗心力衰竭和高血压；它也被提议用于治疗多种心血管疾病。本文综述了醛固酮在细胞水平作用的当前概念。讨论了其在动物模型和人体研究中作为心血管激素的最新发现。我们还描述了醛固酮分离后盐皮质激素受体阻滞剂的发展，并讨论了随后寻找特异性盐皮质激素拮抗剂的过程。此外，我们详细介绍了依普利酮在多种临床情况下的作用，并概述了其潜在的未来应用。
