Greer I A, Thomas G B, Brooks A N
Department of Obstetrics and Gynaecology, University of Glasgow, Royal Infirmary, Scotland.
Reprod Fertil Dev. 1995;7(5):1231-6. doi: 10.1071/rd9951231.
The endothelins are a series of peptides with potent vasoconstrictor effects in vascular tissue; however, they may also have a role as neuroendocrine secretagogues because endothelin and endothelin receptors have been found in hypothalamic and pituitary tissues. Since activation of the fetal hypothalamo-pituitary-adrenal axis is crucial to the process of parturition, the aim of this study was to determine whether endothelin could activate the hypothalamo-pituitary-adrenal axis in the ovine fetus. Catheters were inserted into the carotid artery, jugular vein and lateral cerebral ventricle of six fetal lambs at 118-122 days' gestation. After a 5-day recovery period, endothelin-3 or placebo (saline) was infused intravenously (i.v.) or intracerebroventricularly (i.c.v.) over 30-60 min. The dose of endothelin-3 employed was 0.01 and 0.1 microgram min-1 i.c.v. and 0.1 and 1.0 microgram min-1 i.v. Arterial blood was taken from the fetus before, during and for 1 h after the infusion for measurement of ACTH and cortisol. Blood gas analysis was also performed. Intravenous endothelin-3 produced a dose-dependent increase in ACTH and cortisol concentrations in fetal plasma and was associated with transient fetal hypoxia and acidosis. pH correlated inversely with plasma ACTH (r = -0.701, P < 0.001) and cortisol (r = -0.308, P < 0.001) concentration. An increase in ACTH and cortisol concentrations in fetal plasma was also induced by endothelin-3 administered i.c.v. at 0.1 microgram min-1, and this was not associated with fetal acidosis These data suggest that endothelin administered i.v. will stimulate ACTH and cortisol release indirectly through vasoconstriction and acidosis; however, the response to i.c.v. endothelin administration suggests that it may also act as a central secretagogue for ACTH in the fetus and could therefore play a role in the process of parturition.
内皮素是一类在血管组织中具有强大血管收缩作用的肽；然而，它们也可能作为神经内分泌促分泌素发挥作用，因为在下丘脑和垂体组织中已发现内皮素和内皮素受体。由于胎儿下丘脑 - 垂体 - 肾上腺轴的激活对分娩过程至关重要，本研究的目的是确定内皮素是否能激活绵羊胎儿的下丘脑 - 垂体 - 肾上腺轴。在妊娠118 - 122天的六只胎儿羔羊的颈动脉、颈静脉和侧脑室插入导管。经过5天的恢复期后，在30 - 60分钟内静脉内（i.v.）或脑室内（i.c.v.）注入内皮素 - 3或安慰剂（生理盐水）。所用内皮素 - 3的剂量为脑室内0.01和0.1微克/分钟以及静脉内0.1和1.0微克/分钟。在注入前、注入期间和注入后1小时从胎儿采集动脉血以测量促肾上腺皮质激素（ACTH）和皮质醇。还进行了血气分析。静脉内注入内皮素 - 3使胎儿血浆中ACTH和皮质醇浓度呈剂量依赖性增加，并伴有短暂的胎儿缺氧和酸中毒。pH与血浆ACTH浓度（r = -0.701，P < 0.001）和皮质醇浓度（r = -0.308，P < 0.001）呈负相关。脑室内以0.1微克/分钟注入内皮素 - 3也诱导胎儿血浆中ACTH和皮质醇浓度增加，且这与胎儿酸中毒无关。这些数据表明，静脉内注入内皮素将通过血管收缩和酸中毒间接刺激ACTH和皮质醇释放；然而，对脑室内注入内皮素的反应表明它也可能作为胎儿ACTH 的中枢促分泌素，因此可能在分娩过程中发挥作用。
