Endothelin-1 constricts fetoplacental microcirculation and decreases fetal O2 consumption in sheep.
Endothelin-1 produced by umbilicoplacental tissues may regulate fetal placental perfusion. To investigate its site of action, we measured segmental 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 micrograms/min significantly increased fetal blood pressure in the aorta (+33%), cotyledon artery and vein, and inferior vena cava, and endothelin-1 decreased fetal heart rate (-40%). Vascular resistance in the placental microcirculation increased significantly (+332%), but smaller increases in resistance of the umbilical artery and vein were not significant. Nevertheless, the stiffness of the umbilical arterial wall appeared to increase because vascular input impedance increased significantly both at the heart rate frequency (+85%) and when averaged > 2 Hz (characteristic impedance; +138%). Mean blood flow in the umbilical artery decreased by 64%, and the flow pulsatility index increased 137% (P < 0.05 for both). Despite the large decrease in placental perfusion, there was no significant change in descending aortic oxygen 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 decreases fetal oxygen consumption by an unknown mechanism.
Adamson
S L
SL
Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Whiteley
K J
KJ
Langille
B L
BL
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction
D019332:Endothelin-1