Mazzocchi G, Rebuffat P, Gottardo G, Meneghelli V, Nussdorfer G G
Department of Anatomy, University of Padua, Italy.
Res Exp Med (Berl). 1996;196(3):145-52. doi: 10.1007/BF02576836.
Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular endothelium, which act through two main subtypes of receptors: ETA and ETB. ET-1 is known to stimulate aldosterone (ALDO) secretion by adrenal zona glomerulosa (ZG), and in vitro its effect was recently found to be exclusively mediated by ETB receptors. In this study the involvement of ETA and ETB in the mediation of the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of their selective antagonists BQ-123 and BQ-788, respectively. The bolus intraperitoneal administration of ET-1 dose-dependently raised both basal and angiotensin II (ANG II)-enhanced plasma ALDO concentration (PAC) in rats. Both antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when administered together completely annulled it. Conversely, only BQ-788 reversed the effect of ET-1 on ANG II-enhanced PAC. ET-1 increased systolic blood pressure (BP) in normal rats, but not in animals simultaneously administered ANG II. The hypertensive effect of ET-1 was completely abolished by BQ-123, and not affected by BQ-788. In light of these findings the following conclusions can be drawn: (i) the in vivo ALDO secretagogue action of ET-1 is mediated by both ETA and ETB, this latter subtype of ET receptors playing a major role; and (ii) the mechanism whereby ETA participates in this in vivo effect of ET-1 is indirect, and probably connected with the ET-1-induced rise in BP and adrenal blood flow.
内皮素（ET）是一族血管收缩肽，由血管内皮分泌，通过两种主要的受体亚型起作用：ETA和ETB。已知ET-1可刺激肾上腺球状带（ZG）分泌醛固酮（ALDO），最近发现其体外作用仅由ETB受体介导。在本研究中，分别使用ETA和ETB的选择性拮抗剂BQ-123和BQ-788，研究了ETA和ETB在介导ET-1体内急性促醛固酮分泌作用中的参与情况。腹腔注射大剂量ET-1可使大鼠基础血浆醛固酮浓度（PAC）和血管紧张素II（ANG II）增强的血浆醛固酮浓度呈剂量依赖性升高。两种拮抗剂均能抵消ET-1对基础PAC的刺激作用，同时给药时则完全消除该作用。相反，只有BQ-788能逆转ET-1对ANG II增强的PAC的作用。ET-1可使正常大鼠收缩压（BP）升高，但对同时给予ANG II的动物无此作用。ET-1的升压作用被BQ-123完全消除，而不受BQ-788影响。根据这些发现可得出以下结论：（i）ET-1的体内促醛固酮分泌作用由ETA和ETB共同介导，其中ETB受体亚型起主要作用；（ii）ETA参与ET-1这种体内效应的机制是间接的，可能与ET-1诱导的血压升高和肾上腺血流增加有关。
