Preeclampsia: an imbalance in placental prostacyclin and thromboxane production

Am J Obstet Gynecol. 1985 Jun 1;152(3):335-40. doi: 10.1016/s0002-9378(85)80223-4.

Abstract

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 greater than or equal to 140/90 mm Hg, urinary protein greater than 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 degrees 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 radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1 alpha. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 +/- 4.7 versus 6.3 +/- 1.5 pg/mg/hr, mean +/- SE, p less than 0.01), whereas the production of prostacyclin was significantly decreased (3.0 +/- 0.3 versus 6.7 +/- 0.5 pg/mg/hr, p less than 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 mumol/L) and not affected (p greater than 0.50) by arachidonic acid (100 mumol/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / biosynthesis
  • Adult
  • Arachidonic Acid
  • Arachidonic Acids / pharmacology
  • Culture Media
  • Epoprostenol / biosynthesis*
  • Female
  • Humans
  • Indomethacin / pharmacology
  • Infant, Newborn
  • Placenta / analysis
  • Placenta / drug effects
  • Placenta / metabolism*
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Radioimmunoassay
  • Thromboxane B2 / biosynthesis
  • Thromboxanes / biosynthesis*

Substances

  • Arachidonic Acids
  • Culture Media
  • Thromboxanes
  • Arachidonic Acid
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Epoprostenol
  • Indomethacin