U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies

J Hypertens. 1999 Mar;17(3):389-96. doi: 10.1097/00004872-199917030-00012.


Objectives: To measure in-vitro responses to the thromboxane A2 (TxA2) mimetic U46619 in the fetal placental vasculature of human placentae from normotensive women and those with pre-eclampsia. Furthermore, to compare fetal vascular responses to endothelin-1,5-hydroxytryptamine, potassium chloride (KCl) and prostacyclin (PGI2) in placentae from normal or pre-eclamptic pregnancies.

Methods: Single placental lobules of intact placentae were bilaterally perfused in situ (fetal and maternal) with constant flows of Krebs' solution. Changes in fetal arterial perfusion pressure during intra-arterial infusion of vasoactive agents were recorded. Fetal placental vasoconstrictor concentration response curves were obtained to U46619 (0.01-300 nmol/l), endothelin-1 (0.4-160 nmol/l), KCl (3-300 mmol/l) and 5-hydroxytryptamine (0.03-30 mumol/l). In addition, vasodilator concentration response curves were obtained for PGI2 (1.2-350 nmol/l) in the fetal placental circulation during submaximal increases in perfusion pressure with prostaglandin F2 alpha (PGF2 alpha; 0.7-2.0 mumol/l).

Results: The maximum increase in perfusion pressure caused by U46619 in placentae from normotensive women was 194 +/- 25 mmHg. The maximum response to U46619 was significantly reduced in the placentae from women with pre-eclampsia (104 +/- 21 mmHg). In contrast, there were no differences in constrictor responses to endothelin-1,5-hydroxytryptamine and KCl, or in dilator responses to PGI2 in placentae obtained from either normotensive women or those with pre-eclampsia.

Conclusion: TxA2 receptor-mediated vasoconstriction is reduced in the fetal vasculature of placentae from women with pre-eclampsia, possibly to compensate for the increased levels of TxA2 seen in these conditions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
  • Adolescent
  • Adult
  • Antihypertensive Agents / pharmacology
  • Dinoprost
  • Endothelin-1 / pharmacology
  • Epoprostenol / pharmacology
  • Female
  • Fetus / blood supply*
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hypertension / physiopathology*
  • In Vitro Techniques
  • Oxytocics / pharmacology
  • Placenta / blood supply*
  • Placenta / drug effects
  • Potassium Chloride / pharmacology
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / physiopathology*
  • Serotonin / pharmacology
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology*


  • Antihypertensive Agents
  • Endothelin-1
  • Free Radical Scavengers
  • Oxytocics
  • Vasoconstrictor Agents
  • Serotonin
  • Potassium Chloride
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Dinoprost
  • Epoprostenol