Kirchengast M, Münter K
Department of International Strategic Marketing Cardiovascular, Knoll AG, D-67008 Ludwigshafen, Germany.
Proc Soc Exp Biol Med. 1999 Sep;221(4):312-25. doi: 10.1046/j.1525-1373.1999.d01-88.x.
Endothelins build a peptide family composed of three isoforms, each of them containing 21 amino acids. Endothelin-1 is the isoform mainly responsible for any cardiovascular action and therefore the sole scope of this review. Endothelin-1 is the most potent endogenous vasoconstrictor known; in addition it acts as a potent (co)mitogen. There is a substantial body of experimental evidence that endothelin-1 may contribute not only to sustained vasoconstriction, but also to remodeling within the cardiovascular system. Thus, with the help of endothelin receptor antagonists (available for a few years) the involvement of mainly ETA receptors in structural diseases such as heart failure, pulmonary hypertension, atherosclerosis, restenosis, systemic hypertension, and chronic renal failure has been shown. These data make endothelin receptor antagonists, and especially those selective for the ETA receptor, promising agents for the treatment of chronic cardiovascular diseases associated with remodeling. Currently several chemically distinct, orally available members of this novel class of therapeutic agents are under clinical investigation.
内皮素构成了一个由三种异构体组成的肽家族，每种异构体都含有21个氨基酸。内皮素-1是主要负责任何心血管作用的异构体，因此也是本综述的唯一主题。内皮素-1是已知的最有效的内源性血管收缩剂；此外，它还作为一种强效（共）有丝分裂原起作用。有大量实验证据表明，内皮素-1不仅可能导致持续性血管收缩，还可能参与心血管系统的重塑。因此，借助内皮素受体拮抗剂（已上市数年），已证明主要是ETA受体参与了诸如心力衰竭、肺动脉高压、动脉粥样硬化、再狭窄、系统性高血压和慢性肾衰竭等结构性疾病。这些数据使内皮素受体拮抗剂，尤其是那些对ETA受体具有选择性的拮抗剂，成为治疗与重塑相关的慢性心血管疾病的有前景的药物。目前，这类新型治疗药物中有几种化学结构不同、可口服的成员正在进行临床研究。
