The roles of thromboxane A2 in high salt‐induced defect during pregnancy (832.4)

Abstract

Preeclampsia is a pregnant‐related hypertensive disorder. Affected women might be at risk of developing eclampsia that would cause fetal and maternal death. Several studies have indicated that women suffering from preeclampsia with high levels of thromboxane A2 (TXA2) metabolites in plasma and urine might induce thrombosis and hypertension, and developmental retardation of the placenta. We had clinical data indicating that thromboxane A2 synthase (TXAS) were highly expressed in preeclamptic placenta. To investigate the roles of TXA2 in pregnancy‐related hypertension and preeclampsia, pregnant WT mice and TXA2deficient (TXAS KO) mice were fed with high salt in drinking water. We found that high salt‐treatment induced more severe syndromes in WT than in TXA2‐deficient pregnant mice. Hypertension characterized by significantly increased blood pressure was observed in high salt‐treated WT but not TXA2‐deficient pregnant mice. Compared to normal nonpregnant female mice fed with high salt, pregnant mice with the same treatment had severely decreased maternal body weight, fetal size and fetal weight. High salt feeding also induced cellular apoptosis and suppressed cellular proliferation in the placenta of pregnant but not nonpregnant mice. Moreover, increased abnormal cell degeneration was also observed in the fetuses of WT but not TXA2‐deficient mice. These results demonstrate that deficiency of TXA2 in pregnant mice rendered mice more resistant to high salt‐induced hypertension and growth retardation of placenta and fetus, suggesting a therapeutic potential of inhibitors of the thromboxane pathway for preeclampsia.