Endothelins including its most abundant isoform, endothelin-1 (ET-1), are peptides acting as vasoconstrictors when binding to ETA and ETB receptors, and, in addition to their distinct roles in normal physiology, endothelins have a central role in the pathophysiology of many diseases including cardiovascular and renal diseases. Endothelin-1 (ET-1), the most potent vasoconstrictor in the cardiovascular system, regulates basal vascular tone and glomerular hemodynamics. ET-1 is involved also in vascular and cardiac hypertrophy, inflammation, and in the development and progression of cardiovascular diseases - e.g. essential hypertension, atherosclerosis, coronary artery disease, congestive heart failure, pulmonary arterial hypertension and cerebrovascular disease and renal diseases - e.g. acute renal failure, polycystic kidney disease and chronic kidney disease. Not surprisingly, the ET system has become a target for therapeutic interventions that now include a few already established and some new promising agents. In this narrative review, we summarize physiologic properties of the ET system, focusing especially on ET-1, and its role in the pathophysiology of ET system activated diseases, and discuss the potentials of therapeutic interventions targeting the ET system in cardiovascular and renal diseases. While ET receptor antagonists have already revolutionized the management of idiopathic pulmonary arterial hypertension, so far, this class of drugs have failed as medication for congestive heart failure. Clinical trials continue to explore new applications of endothelin receptor antagonists in treatment-resistant hypertension and chronic kidney disease and have shown some benefits in the latter group by reducing proteinuria; however, they have not been approved yet. We conclude that larger clinical trials are needed to validate the use of ET receptor antagonists in ET system activated diseases.

中文翻译：

---

内皮素系统作为心血管和肾脏疾病治疗干预的目标。

内皮素包括其最丰富的同种型内皮素-1（ET-1），是与ETA和ETB受体结合时起血管收缩剂作用的肽，除了在正常生理学中的独特作用外，内皮素还对内皮素的病理生理起着核心作用。许多疾病，包括心血管和肾脏疾病。内皮素-1（ET-1）是心血管系统中最有效的血管收缩剂，可调节基础血管紧张度和肾小球血流动力学。ET-1还参与血管和心脏肥大，炎症以及心血管疾病（例如原发性高血压，动脉粥样硬化，冠状动脉疾病，充血性心力衰竭，肺动脉高压和脑血管疾病和肾脏疾病）的发展和进程，以及例如急性肾衰竭 多囊肾病和慢性肾脏病。毫不奇怪，ET系统已成为治疗干预的目标，现在包括一些已经建立的治疗剂和一些新的有希望的治疗剂。在本篇叙事综述中，我们总结了ET系统的生理特性，尤其是ET-1，及其在ET系统激活的疾病的病理生理中的作用，并讨论了针对ET系统的心血管和肾脏疾病治疗干预措施的潜力。尽管ET受体拮抗剂已经彻底改变了特发性肺动脉高压的治疗方法，但到目前为止，这类药物作为充血性心力衰竭的药物均无效。临床试验继续探索内皮素受体拮抗剂在抗药性高血压和慢性肾脏疾病中的新应用，并通过减少蛋白尿在后者中显示出某些益处。但是，它们尚未被批准。我们得出结论，需要更大的临床试验来验证ET受体拮抗剂在ET系统激活的疾病中的使用。