Role of gap junction involved with endothelium-derived hyperpolarizing factor for the quercetin-induced vasodilatation in rat mesenteric artery

Aims: Modulation of vasodilating actions by quercetin, a kind of flavonoid, was investigated using rat mesenteric arterial ring strips. Main methods: Ring strips (1 mm) of rat mesenteric artery were used. The specimens were kept at 36.5 degrees C in Krebs-Henseleit solution oxygenated with 95% O-2 and 5% CO2. Key findings: Quercetin (0.1 to 100 mu M ) dilated the contraction induced by norepinephrine (1 mu M) in a concentration-dependent manner. The quercetin-induced vasodilatation was almost resistant to both 100 mu M L-N-G-nitro arginine methyl ester (L-NAME) and 100 mu M indomethacin. At 1 mM tetraethylammonium (a K-Ca channel inhibitor) decreased the quercetin-induced vasodilatation, which was resistant to L-NAME and indomethacin, but not significantly. L-NAME-and indomethacin-resistant quercetin-induced vasodilatation was significantly attenuated by 100 mu M 18 alpha-and 50 mu M 18 beta-glycyrrhetinic acids (gap junction inhibitors). Endothelium removal as well significantly attenuated the vasodilatation to the same extent. Significance: These results indicate that quercetin dilates the mesenteric artery via endothelium-dependent mechanisms, and the dilatation is mainly mediated by gap junctions closely involved with endothelium-derived hyperpolarizing factor (EDHF). (C) 2013 Elsevier Inc. All rights reserved.