THE INFLUENCE OF ENDOTHELIN-1 ON HUMAN FETOPLACENTAL BLOOD-VESSELS - A COMPARISON WITH 5-HYDROXYTRYPTAMINE

1 The vasoconstrictor effect of endothelin-1 (3 x 10(-11) M - 10(-7) M) was studied in successive generations of blood vessels of the foeto-placental vascular tree. These were the human umbilical arteries and veins, primary surface chorionic plate arteries, secondary chorionic plate arteries, tertiary surface chorionic plate arteries and veins and the secondary stem villus arterioles. The responses to endothelin-1 were compared with those to 5-hydroxytryptamine (10(-9) M - 10(-5) M). Arterial preparations were gassed with 2.5% O2, 8% CO2 balance N2 and venous preparations were gassed with 5% O2, 6% CO2 balance N2 to simulate the conditions prevalent in utero. The influence of increasing the oxygen tension to 16% (that prevalent at birth) on the response to endothelin-1 on the umbilical arteries was also investigated. 2 All the arterial vessels tested were some ten times more sensitive to endothelin-1 than to 5-hydroxytryptamine and the venous preparations were ten times more sensitive to endothelin-I than were their equivalent arteries. Increasing oxygen tension did not affect the responses to endothelin-I in the umbilical artery. 3 Whilst the amplitude of the endothelin-1-induced response was uniform throughout the foeto-placental vascular tree, including the stem villus arterioles, the maximum response to 5-hydroxytryptamine decreased with successive generations and it had no significant effect on the stem villus arterioles. The ratios of the responses to 10(-7) M endothelin-1: 10(-7) M 5-hydroxytryptamine in human umbilical arteries, primary surface chorionic plate arteries, secondary chorionic plate arteries, tertiary surface chorionic plate arteries and the secondary stem villus arterioles in the vessels (listed in order of decreasing vessel size) were 1:1.2, 1:0.36, 1:0.33, 1:0.35 and 1:0.04 respectively. 4 In conclusion, endothelin-I is a powerful vasoconstrictor at all levels of the foeto-placental vascular system including the stem villus resistance vessels. It may play an important role in maintaining foeto-plancental vascular resistance at the low oxygen tension which exists in this vascular system in utero.