SEROTONIN-INDUCED VASOCONSTRICTION IS MEDIATED BY THROMBOXANE RELEASEAND ACTION IN THE HUMAN FETAL-PLACENTAL CIRCULATION

The possibility that prostanoids mediate the contractile response of s erotonin on placental vessels was investigated. Rings of chorionic pla te arteries and veins with and without endothelium were suspended in a n organ bath for recording isometric mechanically activity. Serotonin caused dose-dependent contractions that were significantly attenuated by indomethacin (cyclo-oxygenase inhibitor, 10 mu M) and SQ29,548 (thr omboxane receptor antagonist, 1 mu M). Pretreatment of placental venou s and arterial rings with indomethacin decreased sensitivity (EC(50)) to serotonin of 2.3- and 1.9-fold, respectively. Pretreatment with SQ2 9,548 decreased sensitivity to serotonin of twofold in veins and 2.1-f old in arteries. In the endothelium-denuded placental arteries and vei ns, pretreatment with indomethacin and SQ29,548 reduced the serotonin- induced contraction in a similar way to that obtained in the endotheli um-intact vessels. In isolated perfused cotyledon through the fetal ci rculation, serotonin caused a significant increase in perfusion pressu re and stimulated thromboxane release 1.9-fold compared with basal val ues. Therefore, serotonin-induced vasoconstriction in the human fetopl acental circulation appears to be mediated in part by thromboxane rele ase or action. This effect is not dependent on mediators released from the endothelium. The present study provides evidence for the particip ation of thromboxane A, in the contractile response to serotonin in th e human placental circulation. The ability of serotonin to release thr omboxane A, which is also a potent vasoconstrictor agent, may be impor tant in increase fetoplacental resistance, one of the features of pre- eclampsia. (C) 1997 W. B. Saunders Company Ltd.