Characterization of endothelin receptors and localization of 125I-endothelin-1 binding sites in human umbilical artery.

The mechanisms of endothelin-1-induced contractile response in the human umbilical artery were investigated in vitro. Autoradiography revealed 125I-endothelin-1 binding sites in the smooth muscle layer of the vessel wall. Endothelin-1 and sarafotoxin S6b induced concentration-dependent contractions while endothelin-3 was virtually without contractile effect. The endothelin ETA receptor antagonist BQ 123 did not affect the contraction to endothelin-1 but antagonized the contraction to sarafotoxin S6b. The contraction to endothelin-1 and sarafotoxin S6b was diminished by both verapamil and nicardipine. It can be concluded that endothelin-1 is a vasoconstrictor in the human umbilical artery, probably acting via more than one contraction-mediating receptor. The 125I-endothelin-1 binding sites demonstrated in the smooth muscle layer of the vessel may correspond to receptors mediating the contractile effect. The mechanisms of action seems to involve activation of Ca2+ channels. The present study does not give any evidence for interaction of endothelin-1 with other endothelium-derived vasoactive agents in this vessel.