The comparative effects of big endothelin-1, endothelin-1, and endothelin-3 in the human fetal-placental circulation

• Published in: American journal of obstetrics and gynecology Vol. 167; no. 6; p. 1651
• Main Authors: Myatt, L, Brewer, A S, Brockman, D E
• Format: Journal Article
• Language: English
• Published: United States 01.12.1992
• Subjects: Blood Circulation - drug effects; Dose-Response Relationship, Drug; Endothelin-1; Endothelins - pharmacology; Female; Fetus - drug effects; Fetus - physiology; Humans; Perfusion; Placenta - blood supply; Pregnancy; Pressure; Protein Precursors - pharmacology; Regional Blood Flow - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilation
• ISSN: 0002-9378
• DOI: 10.1016/0002-9378(92)91756-Z

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