Serotonin-induced vasoconstriction is mediated by thromboxane release and action in the human fetal-placental circulation.
The possibility that prostanoids mediate the contractile response of serotonin on placental vessels was investigated. Rings of chorionic plate arteries and veins with and without endothelium were suspended in an organ bath for recording isometric mechanically activity. Serotonin caused dose-dependent contractions that were significantly attenuated by indomethacin (cyclo-oxygenase inhibitor, 10 microM) and SQ29,548 (thromboxane receptor antagonist, 1 microM). Pretreatment of placental venous and arterial rings with indomethacin decreased sensitivity (EC50) to serotonin of 2.3- and 1.9-fold, respectively. Pretreatment with SQ29,548 decreased sensitivity to serotonin of twofold in veins and 2.1-fold in arteries. In the endothelium-denuded placental arteries and veins, pretreatment with indomethacin and SQ29,548 reduced the serotonin-induced contraction in a similar way to that obtained in the endothelium-intact vessels. In isolated perfused cotyledon through the fetal circulation, serotonin caused a significant increase in perfusion pressure and stimulated thromboxane release 1.9-fold compared with basal values. Therefore, serotonin-induced vasoconstriction in the human fetoplacental circulation appears to be mediated in part by thromboxane release or action. This effect is not dependent on mediators released from the endothelium. The present study provides evidence for the participation of thromboxane A2 in the contractile response to serotonin in the human placental circulation. The ability of serotonin to release thromboxane A2 which is also a potent vasoconstrictor agent, may be important in increase fetoplacental resistance, one of the features of pre-eclampsia.
Cruz
M A
MA
Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile.
Gallardo
V
V
Miguel
P
P
Carrasco
G
G
González
C
C
D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D011453:Prostaglandins / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D011453:Prostaglandins; D012701:Serotonin; D013928:Thromboxane A2