Endothelin-1-induced vasoconstriction is not mediated by thromboxane release and action in the human fetal-placental circulation.

Abstract

The vasoconstrictor peptide endothelin-1 (8 x 10(-10) to 1 x 10(-8) mol/L) significantly increased fetal-placental perfusion pressure in vitro in a cumulative manner from 30 +/- 2 to 123 +/- 25 mm Hg (mean +/- SEM, n = 5, p less than 0.0005, analysis of variance). Accompanying this vasoconstriction was a corresponding reduction in fetal-placental perfusate flow rate. Measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in the fetal-placental perfusate revealed a significant reduction in their release (p less than 0.0096 and p less than 0.0004, analysis of variance, respectively) when corrected for flow rate. Neither the thromboxane synthesis inhibitor dazoxiben (10(-6) mol/L) nor the thromboxane receptor antagonist SQ29548 (10(-6) mol/L) was able to block the vasoconstrictor actions of endothelin-1. Therefore endothelin-1-induced vasoconstriction in the human fetal-placental circulation does not appear to be mediated by thromboxane release or action. The stimulus to eicosanoid release in the fetal-placental circulation may be hydrodynamic, i.e., flow or shear stress.