Parris R J, Webb D J
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Scotland, UK.
Vasc Med. 1997;2(1):31-43. doi: 10.1177/1358863X9700200106.
Endothelin-1, a member of a novel family of regulatory peptides, is the most potent vasoconstrictor and pressor substance known. Endothelin-1 is a 21-amino-acid endothelium-derived peptide causing uniquely sustained vasoconstriction. In addition, endothelin-1 has pronounced effects on the coronary, renal and cerebral circulations, enhances responses to other vasoconstrictors, and is comitogenic. Recent studies have shown that the endothelins are essential for normal fetal development, and that endothelin-1 plays an important physiological role in the regulation of basal vascular tone and blood pressure in healthy humans. There is now also a wealth of evidence suggesting that endothelin-1 is a key mediator in a range of cardiovascular diseases associated with sustained vasoconstriction, such as chronic heart failure, and with vasospasm, such as subarachnoid haemorrhage. In addition, endothelin-1 appears to act in opposition to nitric oxide to promote the atherosclerotic process. There are a large number of oral and intravenously active endothelin antagonists entering clinical development and a number of clinical studies, particularly with endothelin receptor antagonists, are now under way. Such studies are beginning to define the role of the endothelins in cardiovascular disease and to confirm the potential of the endothelin system as an important new therapeutic target.
内皮素-1是一种新型调节肽家族的成员，是已知最强效的血管收缩剂和升压物质。内皮素-1是一种由21个氨基酸组成的内皮源性肽，可引起独特的持续性血管收缩。此外，内皮素-1对冠状动脉、肾循环和脑循环有显著影响，增强对其他血管收缩剂的反应，并且具有促有丝分裂作用。最近的研究表明，内皮素对正常胎儿发育至关重要，并且内皮素-1在健康人的基础血管张力和血压调节中发挥重要的生理作用。现在也有大量证据表明，内皮素-1是一系列与持续性血管收缩相关的心血管疾病（如慢性心力衰竭）以及与血管痉挛相关的疾病（如蛛网膜下腔出血）中的关键介质。此外，内皮素-1似乎与一氧化氮起相反作用，促进动脉粥样硬化进程。有大量口服和静脉活性内皮素拮抗剂正在进入临床开发阶段，并且一些临床研究，特别是内皮素受体拮抗剂的研究，正在进行中。此类研究开始明确内皮素在心血管疾病中的作用，并证实内皮素系统作为一个重要的新治疗靶点的潜力。
