U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies

Objectives To measure in-vitro responses to the thromboxane A(2) (TXA(2)) mimetic U46619 in the fetal placental vasculature of human placentae from normotensive women and those with pre-eclampsia, Furthermore, to compare fetal vascular responses to endothelin-1, 5-hydroxytryptamine, potassium chloride (KCl) and prostacyclin (PGI(2)) in placentae from normal or pre-eclamptic pregnancies. Methods Single placental lobules of intact placentae were bilaterally perfused in situ (fetal and maternal) with constant flows of Krebs' solution, Changes in fetal arterial perfusion pressure during intra-arterial infusion of vasoactive agents were recorded, Fetal placental vasoconstrictor concentration response curves were obtained to U46619 (0.01-300 nmol/l), endothelin-1 (0.4-160 nmol/l), KCl (3-300 mmol/l) and 5-hydroxytryptamine (0.03-30 mu mol/l). In addition, vasodilator concentration response curves were obtained for PGI(2) (1.2-350 nmol/l) in the fetal placental circulation during submaximal increases in perfusion pressure with prostaglandin F-2 alpha (PGF(2 alpha); 0.7-2.0 mu mol/l). Results The maximum increase in perfusion pressure caused by U46619 in placentae from normotensive women was 194 +/- 25 mmHg. The maximum response to U46619 was significantly reduced in the placentae from women with pre-eclampsia (104 +/- 21 mmHg), In contrast, there were no differences in constrictor responses to endothelin-1, 5-hydroxytryptamine and KCl, or in dilator responses to PGI(2) in placentae obtained from either normotensive women or those with pre-eclampsia. Conclusion TxA(2) receptor-mediated vasoconstriction is reduced in the fetal vasculature of placentae from women with pre-eclampsia, possibly to compensate for the increased levels of TxA(2) seen in these conditions. J Hypertens 1999, 17:389-396 (C) Lippincott Williams & Wilkins.