Glibenclamide Inhibits Agonist-induced Vasoconstriction of Placental Chorionic Plate Arteries.

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. Aim 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 HCO 3 − -buffered physiological salt solution (PSS) at 37 °C (5% O 2 /5% CO 2 bubbling) and normalised at 0.9 of L 5.1 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 ). Results Pre-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. Conclusion 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.