title: Effects of hypoxia on regulation of prostanoid production in decidual endothelial cells in normal and preeclamptic pregnancy.
abstract: OBJECTIVE
  To examine the effect on prostacyclin and thromboxane production of incubating decidual endothelial cells under hypoxic conditions, comparing cells from normal and preeclamptic pregnancies. Furthermore, to determine whether hypoxia is deleterious to cell growth, and test the effects of stimulation and inhibition on prostanoid production.
  
  
  METHODS
  Decidual endothelial cells were exposed for a total of 40 hours to normoxic (20% O2) or hypoxic (2% O2) conditions. Prostacyclin and thromboxane secretion over the final 24 hours of incubation was measured and cell numbers after incubation determined. Lipopolysaccharide (LPS) (1.0 microgram/mL) was used as a stimulator and pirmagrel (1.0 mumol/L) and tranylcypromine (10.0 mumol/L) as prostanoid synthase inhibitors.
  
  
  RESULTS
  Incubations in hypoxia resulted in increased thromboxane (P < .05) but no change in prostacyclin production. This thromboxane increase was abrogated by pirmagrel. LPS caused significant stimulation of prostacyclin and thromboxane secretion and both LPS and hypoxia resulted in lower cell numbers. Decidual endothelial cells from normal and preeclamptic pregnancies were generally not different.
  
  
  CONCLUSIONS
  This study indicates that in preeclampsia, where decidual endothelial cells are in a relatively more hypoxic environment, thromboxane production by these cells is likely to be increased and the prostacyclin/thromboxane ratio decreased. The thromboxane synthase inhibitor, pirmagrel, was able to reverse this abnormal increased secretion of thromboxane in vitro.
authors.affiliation: Department of Renal Medicine, Sydney University at Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Rowe
authors.forename: S
authors.initials: S
authors.lastname: Campbell
authors.forename: E D
authors.initials: ED
authors.lastname: Gallery
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D003656:Decidua / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014191:Tranylcypromine / Q000494:pharmacology
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011725:Pyridines; D014191:Tranylcypromine; D013928:Thromboxane A2; D003577:Cytochrome P-450 Enzyme System; C037787:pirmagrel; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase