Increased thromboxane release in preeclampsia after serotonin-induced placental vasoconstriction

The hypersensitivity in response to many vasoactive agents in preeclampsia (PE) may be mediated by prostanoids. Serotonin (5-HT)-induced vasoconstriction is in part mediated by thromboxane A2 (TXA2) release. The human placenta is able to produce considerable amounts of both thromboxane and prostaglandins. Thus, the eicosanoids may play an important role in the local regulation of blood flow through the fetoplacental unit under normal and pathological conditions. The goal of the study was to evaluate, whether release of TXA2 is altered in PK. Placentas obtained after preeclamptic (n=6; Group I) and normal (n=6; Group II, control) pregnancies delivered at term by cesarean sections were perfused in vitro at 37°C using the modified Cedard manner. Perfusing fluid was saturated with 95% O2 and 5% CO2. Perfusion pressure, measured continuously, was the main parameter of the vascular status changes. Over 120 min, 5-HT (Sigma; 1.0 μmol/l, 2 min increments at 10 ml/min), indomethacin (Sigma; 10 μmol/l, 4 min increments at 10 ml/min) and 5-HT together with indomethacin (1.0 and 10 μmol/l, respectively; given as 2 min infusion at 10 ml/min) were administered. In placental venous blood samples obtained before, during and after vascular reaction the concentrations of thromboxane B2 (TXB2; stable product of unstable TXA2) were estimated immunoenzymatically (ELISA test). 5-HT produces significantly higher (P<0.05) increases in vascular resistance in preeclamptic placentas compared to the control (mean increase of perfusion pressure 1.95±0.11 and 1.47±0.09 kPa, respectively), and this effect correlates with thromboxane concentration (147±21 versus 117±25 pg/ml). Pretreatment with cyclo-oxygenase inhibitor (indomethacin) attenuates contractile response to 5-HT in both groups.