Endothelin‐induced contractions in human placental blood vessels are enhanced in intrauterine growth retardation, and modulated by agents that regulate levels of intracellular calcium.

Abstract

Endothelin-1 (ET-1) is a strongly vasoactive polypeptide that may be involved in the regulation of the uteroplacental blood flow. In the present study we have examined the contractile response to ET-1 in human placental arteries in the presence of several agents that interfere with storage of intracellular calcium, e.g. caffeine, ryanodine and thapsigargin. We have also compared the contractile response to ET-1 in normal pregnancies with that of patients with foetal intrauterine growth retardation (IUGR), a condition with reduced uteroplacental blood flow. We found that the response to ET-1 in the placental arteries from women with normal pregnancies was reduced by 20% in the absence of extracellular calcium. Caffeine relaxed the basal tone of the vessels and reduced the contractile response to ET-1 by 51%. Nifedipine in addition to caffeine resulted in a reduction of 70%. Ryanodine also reduced the tone. Thapsigargin had no effect on the placental arteries at lower concentrations, but gave a progressive and slow contraction at 10(-6) M. The ET-1 induced contraction in placental arteries from IUGR patients was 67% more potent than in placental arteries from women with normal pregnancies, 129% as compared with 77% of the maximal K(+)-induced contraction. We conclude that the ET-1-induced contractile response in the human placental artery is dependent on influx of extracellular calcium as well as mobilization of calcium from intracellular stores. An increased sensitivity to ET-1 in placental arteries may contribute to the reduced uteroplacental blood flow in intrauterine growth retardation.