Effects of vasoactive autacoids on the human umbilical-fetal placental vasculature.

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), F2 alpha (PGF2 alpha), 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 PGF2 alpha 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 support 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.