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 degrees C (5% O(2)/5% CO(2) bubbling) and normalised at 0.9 of L(5.1kPa). Constriction viability was assessed with 120mmoll(-1) potassium solution (KPSS). Dose-response curves were produced with the thromboxane-mimetics U46619 and U44069 (10(-10)-2x10(-6)M), arginine vasopressin (10(-10)-5x10(-8)M) and endothelin-1 (10(-11)-3x10(-7)M) in the presence or absence of 50mumoll(-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 (10mumoll(-1)). RESULTS: Pre-incubation with 50mumoll(-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.[1]References
- Glibenclamide Inhibits Agonist-induced Vasoconstriction of Placental Chorionic Plate Arteries. Wareing, M., Greenwood, S.L., Fyfe, G.K., Baker, P.N., Taggart, M.J. Placenta (2006) [Pubmed]
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