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

OBJECTIVESTo measure in-vitro responses to the thromboxane A2 (TxA2) 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 (PGI2) in placentae from normal or pre-eclamptic pregnancies. METHODSSingle placental lobules of intact placentae were bilaterally perfused in situ (fetal and maternal) with constant flows of Krebsʼ 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 μmol/l). In addition, vasodilator concentration response curves were obtained for PGI2 (1.2–350 nmol/l) in the fetal placental circulation during submaximal increases in perfusion pressure with prostaglandin F2α (PGF2α; 0.7–2.0 μmol/l). RESULTSThe 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 PGI2 in placentae obtained from either normotensive women or those with pre-eclampsia. CONCLUSIONTxA2 receptor-mediated vasoconstriction is reduced in the fetal vasculature of placentae from women with pre-eclampsia, possibly to compensate for the increased levels of TxA2 seen in these conditions.