Characterization, localization and actions of endothelins in umbilical vessels and placenta of man.

Abstract

Endothelin-like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin-like immunoreactivity (0.4-1.4 pmol g-1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin-like immunoreactivity in the amniotic fluid was much higher (77 pmol l-1) than in umbilical cord plasma (10 pmol l-1). Characterization by reverse phase HPLC revealed that most of the endothelin-like immunoreactivity eluted in the position of synthetic endothelin-1 or oxidized endothelin-1. Specific, high affinity binding sites for endothelin-1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin-1 and -3 were almost equipotent as competing ligands for endothelin-1 binding sites, whereas in the umbilical artery endothelin-3 was much less potent than endothelin-1. Scatchard analysis of the binding for placental membranes displayed a straight line (r = -0.994) indicating a single class of endothelin receptors with a Kd-value of 80 pmol l-1 and Bmax of 113 fmol mg-1. Endothelin-1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l-1 while endothelin-3 had no contractile effect up to 10(-7) mol l-1. It is concluded that endothelin-1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin-1 was observed in foetal circulation and amniotic fluid. Endothelin-receptors seem to be of different types in placenta (ETB type) and umbilical vessels (ETA type).