Levin E R
Department of Medicine and Pharmacology, University of California, Irvine, USA.
Am J Nephrol. 1996;16(3):246-51. doi: 10.1159/000169004.
The normal functional state of the vasculature and the events leading to the development of significant arterial disease involve the interaction of important vasoactive substances, which play important modulating or initiating roles in the development of hypertension and arteriosclerosis. Three endothelins have now been identified, of which ET-1 is the best characterized. ET-1 is produced by epithelial, mesangial, neuronal and glial, and liver cells, and is the most potent vasoconstrictor yet found. Each endothelin is derived from a different gene on separate chromosomes, and each binds to at least 2 types of receptor. The plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for adjusting vascular resistance or blood pressure. The actions of endothelin are mediated through several pathways of postreceptor signaling, including activation of the mitogen-activated protein kinase cascade, which give rise to its growth-stimulating properties. Secretion of ET-1 from cultured endothelial cells is stimulated by a wide range of substances, and is inhibited by some prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine vasopressin and atrial natriuretic peptide, and participates in the hormonal control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion, as does insulin, and this could play a role in the accelerated vascular disease of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the development of acute asthma, primary pulmonary hypertension and pulmonary fibrosis. Its role in hypertension is still debatable, though most of the manifestations of congestive heart failure can theoretically be explained by the actions of ET-1. Endothelin also has extensive renovascular and parenchymal effects in the kidney. It is hoped that a fuller understanding of the role of endothelins in normal or pathologic vasculature will lead to effective therapy based on antagonism or augmentation of specific functions.
血管系统的正常功能状态以及导致严重动脉疾病发生的一系列事件，涉及重要血管活性物质之间的相互作用，这些物质在高血压和动脉硬化的发生发展过程中发挥着重要的调节或起始作用。现已鉴定出三种内皮素，其中内皮素 -1（ET -1）的特征最为明确。ET -1由上皮细胞、系膜细胞、神经元和神经胶质细胞以及肝细胞产生，是目前发现的最强效的血管收缩剂。每种内皮素都源自不同染色体上的不同基因，且每种内皮素至少与两种类型的受体结合。ET -1的血浆半衰期约为7分钟，这为调节血管阻力或血压提供了一种快速机制。内皮素的作用是通过受体后信号传导的多种途径介导的，包括丝裂原活化蛋白激酶级联反应的激活，这赋予了其生长刺激特性。培养的内皮细胞分泌ET -1受到多种物质的刺激，并受到一些前列腺素的抑制。内皮素反过来又刺激一氧化氮、精氨酸加压素和心房利钠肽的分泌，并参与盐和水平衡的激素调节。缺氧和缺血会增加ET -1的分泌，胰岛素也会如此，这可能在糖尿病患者加速的血管疾病中起作用。ET -1还会引起支气管收缩，并与急性哮喘、原发性肺动脉高压和肺纤维化的发生有关。其在高血压中的作用仍存在争议，尽管从理论上讲，充血性心力衰竭的大多数表现都可以用ET -1的作用来解释。内皮素在肾脏中也具有广泛的肾血管和实质作用。人们希望对内皮素在正常或病理血管系统中的作用有更全面的了解，从而基于对特定功能的拮抗或增强开发出有效的治疗方法。
