The comparative effects of big endothelin-1, endothelin-1, and endothelin-3 in the human fetal-placental circulation.
OBJECTIVE
This study compared the effects of big endothelin-1, endothelin-1, and endothelin-3 and whether endothelin-converting enzyme was present in the human fetal-placental circulation.


METHODS
Single cotyledons of term placentas were dually perfused in vitro, and increases in fetal-placental perfusion pressure to bolus injections of big endothelin-1, endothelin-1, and endothelin-3 (8 x 10(-10) to 1 x 10(-7) mol/L) were recorded. Responses to big endothelin-1 (10(-7) mol/L) were measured in the same placenta before and after perfusion of the fetal-placental circulation with the neutral metalloprotease inhibitor phosphoramidon (10(-5) mol/L), which acts as an endothelin-converting enzyme inhibitor. All experiments were performed in at least five separate placentas.


RESULTS
Significant concentration-dependent increases in fetal-placental perfusion pressure were seen with endothelin-1 (p < 0.0005), endothelin-3 (p < 0.0256), and big endothelin-1 (p < 0.0034, analysis of variance). Big endothelin-1 always elicited transient vasodilatation before constriction. Phosphoramidon significantly inhibited the vasoconstrictor effect of big endothelin-1 (p < 0.039, paired t test).


CONCLUSIONS
The three endothelins tested are vasoconstrictors, and endothelin-converting enzyme is present in the fetal-placental circulation.
Myatt
L
L
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526.
Brewer
A S
AS
Brockman
D E
DE
D001775:Blood Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010477:Perfusion; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011312:Pressure; D011498:Protein Precursors / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D014662:Vasoconstrictor Agents