ENDOTHELIN-1 CONSTRICTS FETOPLACENTAL MICROCIRCULATION AND DECREASES FETAL O-2 CONSUMPTION IN SHEEP

Endothelin-1 produced by umbilicoplacental tissues may regulate fetal placental perfusion. To investigate its site of action, we measured se gmental resistance in this bed in unanesthetized fetal sheep near term during fetal endothelin-1 infusion. A 15-min intravenous infusion of endothelin-1 at 1 mu g/min significantly increased fetal blood pressur e in the aorta (+33%), cotyledon artery and vein, and inferior vena ca va, and endothelin-1 decreased fetal heart rate (-40%). Vascular resis tance in the placental microcirculation increased significantly (+332% ), but smaller increases in resistance of the umbilical artery and vei n were not significant. Nevertheless, the stiffness of the umbilical a rterial wall appeared to increase because vascular input impedance inc reased significantly both at the heart rate frequency (+85%) and when averaged >2 Hz (characteristic impedance; +138%). Mean blood flow in t he umbilical artery decreased by 64%, and the flow pulsatility index i ncreased 137% (P < 0.05 for both). Despite the large decrease in place ntal perfusion, there was no significant change in descending aortic o xygen tension or oxygen content, because fetal oxygen consumption was reduced by 40%. We conclude that endothelin-1 is a potent constrictor of the placental microcirculation in sheep. Endothelin-1 also decrease s fetal oxygen consumption by an unknown mechanism.