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 × 10^-10 to 1 × 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.