Agapitov Alexei V, Haynes William G
Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA.
J Renin Angiotensin Aldosterone Syst. 2002 Mar;3(1):1-15. doi: 10.3317/jraas.2002.001.
Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor antagonism in human diseases.
内皮素是一族肽类，包括内皮素 -1（ET -1）、内皮素 -2（ET -2）和内皮素 -3（ET -3），每种均含21个氨基酸。ET -1是一种主要由血管内皮细胞分泌的肽，是血管系统中表达的主要异构体，也是目前已知最强效的血管收缩剂。ET -1还具有变力性、趋化性和促有丝分裂特性。此外，它通过对肾素 - 血管紧张素 - 醛固酮系统（RAAS）、血管加压素和心房利钠肽的作用影响盐和水平衡，并刺激交感神经系统。内皮素的总体作用是升高血压和血管张力。因此，内皮素拮抗剂可能在治疗与局部或全身血管收缩及细胞增殖相关的心脏、血管和肾脏疾病中发挥重要作用，如原发性高血压、肺动脉高压、慢性心力衰竭和慢性肾衰竭。长期抗内皮素治疗可能改善症状并有利地改变心力衰竭的进展。内皮素似乎参与硬化性肾脏改变的诱导和进展，导致进展至终末期肾病。除了已知的抑制RAAS的益处外，抗内皮素治疗可能在预防慢性肾衰竭进展方面提供额外益处。临床试验已证明内皮素拮抗剂对原发性高血压、肺动脉高压和心力衰竭患者有潜在的重要益处。需要进一步研究以确定抗内皮素治疗在心血管疾病治疗中的作用，并确定选择性受体拮抗与混合ET（A/B）受体拮抗在人类疾病中的不同作用。
