Webb D J, Strachan F E
Clinical Pharmacology Unit and Research Centre, The University of Edinburgh, Western General Hospital, Scotland.
Am J Hypertens. 1998 Apr;11(4 Pt 3):71S-79S. doi: 10.1016/s0895-7061(98)00003-x.
Endothelin-1, discovered in 1988, is a 21-amino-acid peptide and currently the most potent vasoconstrictor and pressor substance known. Generated by vascular endothelial cells in response to a variety of chemical and mechanical signals, endothelin-1 is known to potentiate the actions of other vasoconstrictor substances and act as a comitogen in addition to directly causing vasoconstriction. There is evidence that endothelin-1 may contribute to the pathophysiology of conditions associated with sustained vasoconstriction, such as hypertension and heart failure, vasospastic conditions, such as subarachnoid hemorrhage, and atherogenesis. Studies using endothelin receptor antagonists show that endothelin-1 plays an important role in the maintenance of vascular tone and blood pressure in healthy humans, predominantly via an effect on the vascular smooth muscle ETA receptors. The endothelin receptor antagonist bosentan also effectively lowers blood pressure in hypertensive subjects and produces sustained and favorable effects on systemic and pulmonary hemodynamics in patients with chronic heart failure. A good side-effect profile, together with a potential for inhibition of atherogenesis, makes the endothelin receptor antagonists a potentially interesting class of novel agents for the treatment of cardiovascular disease.
内皮素 -1于1988年被发现，是一种由21个氨基酸组成的肽，是目前已知的最有效的血管收缩剂和升压物质。内皮素 -1由血管内皮细胞响应各种化学和机械信号而产生，已知它可增强其他血管收缩物质的作用，并除了直接引起血管收缩外，还可作为一种促有丝分裂原。有证据表明，内皮素 -1可能参与与持续性血管收缩相关疾病的病理生理过程，如高血压和心力衰竭、血管痉挛性疾病（如蛛网膜下腔出血）以及动脉粥样硬化的形成。使用内皮素受体拮抗剂的研究表明，内皮素 -1在维持健康人的血管张力和血压方面起着重要作用，主要是通过对血管平滑肌ETA受体的作用。内皮素受体拮抗剂波生坦也能有效降低高血压患者的血压，并对慢性心力衰竭患者的全身和肺血流动力学产生持续且有益的影响。良好的副作用谱以及抑制动脉粥样硬化的潜力，使内皮素受体拮抗剂成为一类潜在的用于治疗心血管疾病的新型药物。
