Endothelin and endothelin receptors in the renal and cardiovascular systems
Endothelin and endothelin receptors in the renal and cardiovascular systems
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DOI：
10.1016/j.lfs.2012.03.026
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发表时间：
2012-10-15
期刊：
影响因子：
6.1
通讯作者：
Emoto, Noriaki
中科院分区：
文献类型：
--
作者：
Vignon-Zellweger, Nicolas;Heiden, Susi;Emoto, Noriaki
内皮素-1(ET-1)是一种多功能激素，调节心血管和肾脏的生理功能。ET-1调节心脏收缩能力、全身和肾脏血管阻力、盐和水肾重吸收，以及肾小球功能。ET-1负责多种细胞事件：收缩、增殖、凋亡等。这些作用发生在两个内皮素受体ETA和ETB激活后，这两个受体存在于肾脏的心肌细胞、成纤维细胞、血管内皮细胞、肾小球和肾小管细胞等。根据受体类型、细胞类型和生理状态的不同，复杂和众多的细胞内通路在功能反应方面可能是相互矛盾的。许多疾病都有增强的ET-1表达，这是其病理生理学的一部分。然而，内皮素阻滞剂的使用目前仅限于肺动脉高压，以及最近对指端溃疡的使用。内皮素系统的复杂性不利于将分子知识转化为临床应用。内皮素拮抗剂可以预防疾病的发展，但次要的不良影响限制了它们的使用。然而，随着对ET-I对心脏和肾脏生理影响的认识不断加深，内皮素系统仍然是一个有希望的治疗靶点。(C)2012 Elsevier Inc.保留所有权利。
Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic and renal vascular resistance, salt and water renal reabsorption, and glomerular function. ET-1 is responsible for a variety of cellular events: contraction, proliferation, apoptosis, etc. These effects take place after the activation of the two endothelin receptors ETA and ETB, which are present - among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial cells, glomerular and tubular cells of the kidney. The complex and numerous intracellular pathways, which can be contradictory in term of functional response depending on the receptor type, cell type and physiological situation, are described in this review. Many diseases share an enhanced ET-1 expression as part of the pathophysiology. However, the use of endothelin blockers is currently restricted to pulmonary arterial hypertension, and more recently to digital ulcer. The complexity of the endothelin system does not facilitate the translation of the molecular knowledge to clinical applications. Endothelin antagonists can prevent disease development but secondary undesirable effects limit their usage. Nevertheless, the increasing understanding of the effects of ET-I on the cardiac and renal physiology maintains the endothelin system as a promising therapeutic target. (c) 2012 Elsevier Inc. All rights reserved.