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. STUDY DESIGN: 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). CONCLUSION: The three endothelins tested are vasoconstrictors, and endothelin-converting enzyme is present in the fetal-placental circulation.