Noll G, Wenzel R R, Lüscher T F
Cardiovascular Research University Hospital, Bern, Switzerland.
Mol Cell Biochem. 1996;157(1-2):259-67. doi: 10.1007/BF00227908.
Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor beta 1 stimulate the formation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ET(B) receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases. Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.
内皮素-1是一种最近发现的主要由内皮细胞释放的肽。缺氧、缺血以及多种因素，如血管紧张素II、凝血酶和转化生长因子β1，均可刺激该肽的形成。另一方面，一氧化氮和心房利钠肽通过环磷酸鸟苷的形成抑制内皮素的合成。内皮素-1从内皮细胞释放后，介导短暂的血管舒张，随后是强烈而持久的血管收缩。内皮素也是平滑肌增殖的促有丝分裂原。内皮素通过激活特定受体发挥其生物学作用。已从哺乳动物组织中克隆出两种不同的受体（ET(A)和ET(B)受体）。在血管平滑肌细胞上，两种受体均介导收缩。内皮细胞仅表达与一氧化氮形成和/或前列环素形成相关的ET(B)受体。在多种疾病中，如肺动脉高压、动脉硬化、肾衰竭、急性冠状动脉综合征、心力衰竭、偏头痛和血管疾病，均已发现血浆内皮素-1浓度升高。最近，已合成了越来越多的内皮素受体拮抗剂，这些拮抗剂已被证明可抑制内皮素介导的血管收缩。目前正在进行临床研究，以阐明内皮素的病理生理作用以及在不同疾病状态下阻断该系统的潜在益处。
