THE EFFECTS OF DIHYDRALAZINE, LABETALOL AND MAGNESIUM-SULFATE ON THE ISOLATED, PERFUSED HUMAN PLACENTAL COTYLEDON

Objective To assess the effects of dihydralazine, labetalol and magnes ium sulphate on the vascular tone in the isolated, perfused human plac ental cotyledon.Methods In vitro perfusion of the fetal compartment of isolated, human placental cotyledons. Results None of the drugs affec ted basal vascular tone. The thromboxane A(2)-mimic U46619 and endothe lin-1 induced a concentration-dependent increment in perfusion pressur e, while 5-hydroxytryptamine induced a variable increase, and norepine phrine induced a small, transient increase in perfusion pressure. Afte r preconstriction with U46619, magnesium sulphate (1.5 x 10(-3) to 6 x 10(-3) mol/l) induced a decrease in perfusion pressure, while dihydra lazine (10(-6) to 10(-4) mol/l) or labetalol (10(-7) to 10(-4) mol/l) enhanced the perfusion pressure. These effects of dihydralazine and la betalol were unaffected by treatment with indomethacin 10(-6) mol/l, b ut could be reversed by addition of magnesium sulphate 6 x 10(-3) mol/ l. Labetalol 10(-6) to 10(-4) mol/l also caused an increase in the per fusion pressure induced by endothelin-1, but showed no effects after p reconstriction with 5-hydroxytryptamine. Pretreatment with labetalol 1 0(-4) mol/l inhibited the transient increase in perfusion pressure ind uced by norepinephrine 3 x 10(-5) mol/l. Conclusions The present data demonstrated that the commonly used vasodilating agents labetalol and dihydralazine do not produce vasodilatation in the human perfused coty ledon after vasoconstriction induced by agents of suggested importance for maintenance of fetal placental vascular tone, and that high conce ntrations of these drugs may even enhance vasoconstriction induced by thromboxane and endothelin-1 in this area. Magnesium sulphate may show the potential to reverse such unwanted effects of dihydralazine and l abetalol.