ENDOTHELIN-1 AND ENDOTHELIN-3 AND BIG ENDOTHELIN-1 CONTRACT ISOLATED HUMAN PLACENTAL VEINS

Experiments were designed to investigate the reactivity of vascular smooth muscle to endothelins (ETs) in veins taken from human placentas immediately after delivery. The placental veins were cut into rings and suspended between two stirrups in conventional organ chambers (filled with aerated, modified Krebs-Ringer bicarbonate solution) for isometric recording of tension. ET-1 and ET-3 caused concentration-dependent contractions of the isolated human placental veins. The responses induced by ET-1 were greater than those evoked by ET-3 and were not significantly affected by BQ-123, a selective inhibitor of ETA receptors. Contractions to big ET-1 were obtained in rings both with and without endothelium; they were inhibited by phosphoramidon, an inhibitor of endothelin-converting enzyme. These findings indicate that the conversion of the precursor of ET-1 can occur in human placental veins. The receptors mediating the contraction of human placental veins to endothelins do not belong to the ETA subtype; the response to the peptides is probably mediated in part by an uncharacterized ET-receptor subtype and in part by ETB receptors. The output of big ET-1 in the vascular wall or from surrounding tissues in the placenta could be involved in the regulation of venous tone in this organ.