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Preeclampsia: An imbalance in placental prostacyclin and thromboxane Production

  • Scott W. Walsh
    Correspondence
    Reprint requests: Dr. Scott W. Walsh, University of Texas Medical School, Department of Obstetrics, Gynecology and Reproductive Sciences, 6431 Fannin, Suite 3.270, Houston, TX 77030.
    Affiliations
    Department of Physiology, Michigan State University, East Lansing, Michigan
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      Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow, and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating, and uterine-activating actions of thromboxane, we considered the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure 140190 mm Hg, urinary protein >0.3 gm/24 hr). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37° C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for thromboxane by radiommunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 ± 4.7 versus 6.3 ± 1.5 pglmglhr, mean ± SE, p < 0.01), whereas the production of prostacyclin was significantly decreased (3.0 ± 0.3 versus 6.7 ± 0.5 pglmglhr, p < 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 [,mol/L) and not affected (p > 0.50) by arachidonic acid (100 µmol/L). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation, and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces seven times more thromboxane than prostacyclin.

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