summary Studies have been made of the effects of autacoids on vascular tone of the human perfused fetal umbilical vein and placental lobule. The thromboxane A2 (TxA2)‐mimetic substance U46619, 5‐hydroxytryptamine and bradykinin were powerful constrictors of the vein. Prostaglandins E2 (PGE2), F2α(PGF2α), adrenaline, noradrenaline, histamine and angiotensin II were much less potent. Venoconstriction caused by U46619, bradykinin and 5‐hydroxytryptamine was reduced during inhibition of phospholipase A2 with mepacrine. Responses to U46619 were also reduced after inhibition of cyclo‐oxygenase with indomethacin whereas those to bradykinin and 5‐hydroxytryptamine were potentiated. In the placenta U46619 was the most potent vasoconstrictor, bradykinin, 5‐hydroxytryptamine, angiotensin II, PGE2 and PGF2α being 10–100 times less active. Responses to U46619 were reduced by either mepacrine or indomethacin. Arachidonic acid caused umbilical venoconstriction but vasodilatation in the placenta. Both effects were reduced by indomethacin. Prostacyclin (PGI2) caused vasodilatation in both preparations. It is suggested that TxA2 in the placenta and TxA2, 5‐hydroxytryptamine and bradykinin in the umbilical vein could contribute to control of vascular smooth muscle tone. Their vasoconstrictor effects are partly indirect and affected by the concomitant local release of eicosanoids. The results add suort to previous conclusions that these autacoids may normally have important influences on blood flow in the fetal extra‐corporeal circulation. Agents inhibiting their synthesis, eg non‐steroidal anti‐inflammatory agents, should only be prescribed during pregnancy with these facts in mind.

An in vitro examination has been made of the thromboxane A2 receptors in human fetal placental villous vessels and umbilical veins utilizing the TxA2 agonist U46619 and its competitive antagonist AH22921. U46619 was a potent constrictor of both preparations. The EC50 were 25.3 nmol/l (s.e.m. = 2.5, n = 8) for causing constriction of perfused villous vessels and 22 nmol/l (s.e.m. = 5, n = 17) for contraction of the venous longitudinal strip. AH22921 competitively antagonized responses to U46619 in both preparations. The pA2 values were not significantly different and their 95% confidence limits, obtained for its ability to antagonize responses to U46619 in villous vessels and the umbilical vein, were 8.0 (7.3-8.8) and 7.1 (6.3-7.9) respectively. It is concluded that TxA2 receptors in both the human fetal placental villous vessels and umbilical vein may be similar. They also may be similar to those in human platelets and pulmonary blood vessels.

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