Role of mineralocorticoid receptor antagonists in cardiovascular disease.
Role of mineralocorticoid receptor antagonists in cardiovascular disease.
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DOI：
10.1161/circresaha.116.302706
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发表时间：
2015-01-02
影响因子：
20.1
通讯作者：
Schiffrin EL
中科院分区：
文献类型：
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作者：
Ferrario CM;Schiffrin EL
醛固酮通过激活心尖上皮钠通道(ENaC)和底侧Na+/K+ATPase泵来控制远端小管水平的钠排泄，从而发挥其最著名的钠稳态作用。最近，这种矿物皮质激素已被证明对心脏和血管起作用。与盐状态有关的醛固酮过量释放会导致基因组和非基因组效应，这些效应通过促进内皮功能障碍以及血管和心肾不利重构，导致高血压、心力衰竭、心肌梗死和慢性肾功能衰竭的靶器官损害。盐皮质激素受体阻滞剂已被证明在难治性高血压和延缓心力衰竭进展以及在实验动物中的动脉粥样硬化发展方面非常有效。越来越多的证据表明，阻断醛固酮和其他潜在的盐皮质激素的作用对不同形式的心血管疾病是一种非常有益的治疗方法。这篇综述总结了有关醛固酮在心血管系统中作用的现有知识，并在向临床领域提供这些知识的翻译影响的同时，说明在探索盐皮质激素受体阻滞剂在心脏、肾脏和血管疾病的较晚期阶段的使用方面还需要取得更多的成就。
Aldosterone exerts its best known sodium homeostasis actions by controlling sodium excretion at the level of the distal tubules via activation of the apical epithelial sodium channel (ENaC) and the basolateral Na+/K+ ATPase pump. Recently, this mineralocorticoid hormone has been demonstrated to act on the heart and blood vessels. Excess release of aldosterone in relation to the salt status induces both genomic and non-genomic effects that by promoting endothelial dysfunction, and vascular and cardio-renal adverse remodeling, contribute to the target organ damage found in hypertension, heart failure, myocardial infarction and chronic renal failure. Mineralocorticoid receptor blockers have been shown to be highly effective in resistant hypertension and to slow down heart failure progression, and in experimental animals, the development of atherosclerosis. Blockade of the action of aldosterone and potentially other mineralocorticoid steroids has been increasingly demonstrated to be an extremely beneficial therapy in different forms of cardiovascular disease. This review provides a summary of the knowledge that exists regarding aldosterone actions in the cardiovascular system and, in providing the translational impact of this knowledge to the clinical arena, illustrates how much more needs to be achieved in exploring the use of mineralocorticoid receptor blockers in less advanced stages of heart, renal, and vascular disease.