[Endothelin--possible significance in pregnancy and hypertensive pregnancy]

Endothelin (ET) is the most potent endogenous vasoconstrictory substance known. There are three structurally and pharmacologically separate endothelial isopeptides in humans; Endothelin-1 is exclusively produced in the vascular endothelium. It seems likely that ET acts as a local paracrine signal rather than a circulating hormone. The synthesis and release of ET is stimulated among others by hypoxia, thrombin and endotoxin. Its effects are mediated by specific, membrane-bound receptors, which are detectable in high concentrations in the fetoplacental tissue. ET-1 causes an initial transient fall in blood pressure, followed by a strong, long-lasting increase in peripheral resistance and blood pressure. Plasma ET-1 levels are increased in preeclampsia as compared to those of normal pregnancies, and do not correlate with mean arterial blood pressure and degree of proteinuria. In umbilical cord blood ET-1 concentrations are 2.5-10-fold higher than those of maternal plasma. Determination of plasma ET is unlikely to be of value in the prediction of the disease. ET-1 induces an increased synthesis of vasodilatory prostaglandins (PGI2, PGE2) and an increased production of endothelial-derived relaxing factor (EDRF); thromboxane concentrations in blood are elevated by thrombin-induced activation of platelets. In animal models ET-1 causes an activation of plasmatic coagulation with consecutive hypercoagulability. In preeclampsia ET may play an important role in the regulation of the endothelial balance. Future therapeutic approaches may include the development of effective ET-antibodies or of inhibitors of the endothelin-converting enzyme.