Glibenclamide Inhibits Agonist-induced Vasoconstriction of Placental Chorionic Plate Arteries

BackgroundPreliminary data suggest that KATP 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.AimTo assess the effect of glibenclamide on placental chorionic plate arterial vasoconstriction.MethodsArteries 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 °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 × 10−6 M), arginine vasopressin (10−10–5 × 10−8 M) and endothelin-1 (10−11–3 × 10−7 M) in the presence or absence of 50 μmol 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 μmol l−1).ResultsPre-incubation with 50 μmol 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.ConclusionGlibenclamide'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.