title: U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, New South Wales, Australia. mdmar@mail.newcastle.edu.au
authors: M A
authors: MA
authors: Read
authors: I M
authors: IM
authors: Leitch
authors: W B
authors: WB
authors: Giles
authors: A M
authors: AM
authors: Bisits
authors: A L
authors: AL
authors: Boura
authors: W A
authors: WA
authors: Walters
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D015237:Dinoprost; D019332:Endothelin-1 / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000098:blood supply*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D010120:Oxytocics / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D016166:Free Radical Scavengers; D010120:Oxytocics; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D011464:Epoprostenol