Drug actions in preeclampsia: Aspirin, but not magnesium chloride or dihydralazine, differentially inhibits cultured human trophoblast release of thromboxane and prostacyclin without affecting angiotensin II, endothelin-1, or leukotriene B4 secretion

Objective: We hypothesized that aspirin, Mg++, and dihydralazine affect the release of vasoactive agents from cultured human placental trophoblast. Study Design: Cytotrophoblasts isolated from placentas of preterm or term deliveries of 14 healthy control women and 15 preeclamptic women were cultured in Dulbeccoʹs modified Eagleʹs medium for 5 days in the presence or absence of either 0.1 mmol/L aspirin, 3 mmol/L magnesium chloride, or 136 ng/ml dihydralazine. Vasoactive substances were quantitated by radioimmunoassay with mean±SEM percentage of untreated cells (=100%) compared by the Mann-Whitney U test and analysis of variance. Results: Aspirin inhibited (p<0.01) both thromboxane and prostacyclin on days 1 and 2 in culture but not on days 3 to 5 unless the Dulbeccoʹs modified Eagleʹs medium was supplemented with arachidonic acid. Aspirin inhibition was greater (p<0.01) for thromboxane in cells cultured 24 hours after preeclamptic pregnancy (preterm 29.9%±6.8%, term 20.1%±5.9%) compared with normal controls (preterm 66.3%±10.6%, term 68.9%±11.6%). Aspirin reduced (p<0.01) the ratio of thromboxane to prostacyclin in media of cells from preeclampsia (untreated 27.8±7.2, aspirin 13.3±4.4), but aspirin had no effect on this ratio in cultures from control normal pregnancies (untreated 6.8±2.9, aspirin 4.8±1.1). Neither magnesium chloride nor dihydralazine affected trophoblast prostanoid production, and no drug altered the media levels of angiotensin II, endothelin-1, or leukotriene B4. Conclusion: Aspirin selectively inhibits trophoblast prostanoid production. This inhibition depends on the availability of arachidonic acid and the presence or absence of preeclampsia. Magnesium and dihydralazine effects in pregnancy are not related to altered release of trophoblast vasoactive compounds.