title: Glibenclamide inhibits agonist-induced vasoconstriction of placental chorionic plate arteries.
abstract: BACKGROUND
  Preliminary data suggest that K(ATP) channels may be expressed in placental arteries and veins [Wareing M, Turner C, Greenwood SL, Baker PN, Fyfe GK. Expression of mRNA encoding K+ channels in chorionic plate arteries and veins. J Soc Gynecol Investig 2004;11:353A]. However, no data exist on glibenclamide's effects in placental chorionic plate arteries.
  
  
  OBJECTIVE
  To assess the effect of glibenclamide on placental chorionic plate arterial vasoconstriction.
  
  
  METHODS
  Arteries were dissected from placental chorionic plate biopsies obtained at term from uncomplicated pregnancies (N=63). Arteries were mounted onto a wire myograph in HCO3- -buffered physiological salt solution (PSS) at 37 degrees C (5% O2/5% CO2 bubbling) and normalised at 0.9 of L5.1 kPa. Constriction viability was assessed with 120 mmol l(-1) potassium solution (KPSS). Dose-response curves were produced with the thromboxane-mimetics U46619 and U44069 (10(-10)-2 x 10(-6)M), arginine vasopressin (10(-10)-5 x 10(-8)M) and endothelin-1 (10(-11)-3 x 10(-7)M) in the presence or absence of 50 micromol l(-1) glibenclamide. The effect of glibenclamide on arginine vasopressin- and U46619-induced constriction was also assessed in the presence of the cyclo-oxygenase inhibitor indomethacin (10 micromol l(-1)).
  
  
  RESULTS
  Pre-incubation with 50 micromol l(-1) glibenclamide significantly right-shifted dose-response curves to all vasoconstrictive agonists tested (repeated measures ANOVA). Indomethacin did not modify the inhibitory effect of glibenclamide.
  
  
  CONCLUSIONS
  Glibenclamide's effects on agonist-induced constrictions are unlikely to be via an inhibition of ATP-sensitive K+ channels, and with U46619- and U44069-induced constrictions, glibenclamide may be acting as a competitive antagonist of thromboxane receptors.
authors: Maternal and Fetal Health Research Centre, University of Manchester, St. Mary's Hospital, Hathersage Road, Manchester, M13 0JH, UK. mark.wareing@manchester.ac.uk
authors: M
authors: M
authors: Wareing
authors: S L
authors: SL
authors: Greenwood
authors: G K
authors: GK
authors: Fyfe
authors: P N
authors: PN
authors: Baker
authors: M J
authors: MJ
authors: Taggart
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D001127:Arginine Vasopressin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D002824:Chorionic Villi / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D021041:Placental Circulation / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000819:agonists; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C028429:U 44069; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005905:Glyburide; D007213:Indomethacin