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)) m imetic U46619 in the fetal placental vasculature of human placentae from no rmotensive women and those with pre-eclampsia, Furthermore, to compare feta l vascular responses to endothelin-1, 5-hydroxytryptamine, potassium chlori de (KCl) and prostacyclin (PGI(2)) in placentae from normal or pre-eclampti c pregnancies. Methods Single placental lobules of intact placentae were bilaterally perfu sed in situ (fetal and maternal) with constant flows of Krebs' solution, Ch anges in fetal arterial perfusion pressure during intra-arterial infusion o f vasoactive agents were recorded, Fetal placental vasoconstrictor concentr ation 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 obtain ed for PGI(2) (1.2-350 nmol/l) in the fetal placental circulation during su bmaximal 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 plac entae from normotensive women was 194 +/- 25 mmHg. The maximum response to U46619 was significantly reduced in the placentae from women with pre-eclam psia (104 +/- 21 mmHg), In contrast, there were no differences in constrict or responses to endothelin-1, 5-hydroxytryptamine and KCl, or in dilator re sponses to PGI(2) in placentae obtained from either normotensive women or t hose with pre-eclampsia. Conclusion TxA(2) receptor-mediated vasoconstriction is reduced in the feta l vasculature of placentae from women with pre-eclampsia, possibly to compe nsate for the increased levels of TxA(2) seen in these conditions. J Hypert ens 1999, 17:389-396 (C) Lippincott Williams & Wilkins.