Contractile effect of endothelin in human placental veins: Role of endothelium prostaglandins and thromboxane

Abstract

Objective: The aim was to study the effects of endothelin-1 on human placental veins and the role of cyclooxygenase products as mediators of these effects. Study design: Rings of placental veins with and without endothelium were suspended in organ chambers filled with physiologic salt solution. After a period of stabilization at optimal basal tension, isometric tensions in the control group were recorded at increasing concentrations of endothelin-1 (10-10 to 10-7 mol/L). Rings in the experimental groups were treated with either indomethacin (cyclooxygenase inhibitor, 10-5 mol/L), dazoxiben (thromboxane synthetase inhibitor, 10-4 mol/L), or SQ29548 (thromboxane receptor antagonist 10-6 mol/L) before addition of endothelin-1. To demonstrate the presence of functional thromboxane receptors in the rings, contractile responses to U-46619 (10-9 to 10-6 mol/L), a thromboxane A2 analog were measured. The effectiveness of SQ29548 blockade was tested in rings treated with SQ29548 (10-6 mol/L) before addition of U-46619. The concentration-response curves of the treated and control groups were compared with the Student paired t test. Results: Endothelin-1 in doses of 10-10 to 10-7 mol/L caused concentration-dependent contraction of placental veins. Indomethacin significantly reduced the response of veins with endothelium to low endothelin-1 concentrations (10-9.5 to 10-9 mol/L), (p < 0.05). However, it had no effect at higher endothelin-1 concentrations or in vessels without endothelium. The presence of functional thromboxane A2 receptors was confirmed by the vasoconstrictor effect of U-46619 and its blockade by treatment with SQ29548. Neither SQ29548 nor the thromboxane A2 synthesis inhibitor dazoxiben significantly influenced the response to endothelin-1. Conclusions: These results demonstrated that endothelin-1 is a potent vasoconstrictor in the human placental vein. Although functional thromboxane A2 receptors exist in this vessel, endothelin-1 is action is independent of thromboxane A2. Prostaglandins may mediate part of the endothelin-1-induced placental vasoconstriction. However, endothelin-1 acts primarily by a direct effect on vascular smooth muscle cells.