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

Abstract

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. 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. 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. 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's 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.