Vol. 302, Issue 1, 66-72, July 2002

Endothelium-Independent Vasodilator Effects of the Flavonoid Quercetin and Its Methylated Metabolites in Rat Conductance and Resistance Arteries

Francisco Pérez-Vizcaíno, Manuel Ibarra, Angel L. Cogolludo, Juan Duarte, Francisco Zaragozá-Arnáez, Laura Moreno, Gustavo López-López and Juan Tamargo

Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid (F.P-V., A.L.C, F.Z-A., L.M., J.G.L-L.); Department of Pharmacology, School of Pharmacy, University of Alcalá, Madrid (M.I.); and Department of Pharmacology, School of Pharmacy, University of Granada, Granada (J.D.), Spain

The flavonoid quercetin is metabolized into isorhamnetin, tamarixetin, and kaempferol, the vascular effects of which are unknown. In the present study, the effects of quercetin and its metabolites were analyzed on isometric tension in isolated rat thoracic and abdominal aorta, in isolated intact and -escin-permeabilized iliac arteries, and on perfusion pressure in the isolated mesenteric resistance vascular bed. In noradrenaline-precontracted vessels, the four flavonoids produced a vasodilator effect, which was inversely correlated with the diameter of the vessel studied; i.e., quercetin, isorhamnetin, tamarixetin, and kaempferol were 5-, 25-, 4-, and 6-fold, respectively, more potent in the resistance mesenteric bed (log IC₅₀ = 5.35 ± 0.15, 5.89 ± 0.11, 5.34 ± 0.10, and 5.66 ± 0.06, respectively) than in the thoracic aorta (log IC₅₀ = 4.68 ± 0.08, 4.61 ± 0.08, 4.73 ± 0.11, and 4.81 ± 0.13, respectively; n = 4-6). The vasodilator responses of quercetin and isorhamnetin were not significantly modified after removal of the endothelium in the thoracic aorta or in the mesenteric bed. Furthermore, the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10⁶ M), the adenylate cyclase inhibitor SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine; 10⁶ M], KCl (40 mM), or ouabain (10³ M) had no effect on isorhamnetin-induced vasodilation in the mesenteric bed. In permeabilized iliac arteries stimulated with Ca²⁺ (pCa of 5.9), isorhamnetin was also significantly more potent (log IC₅₀ = 5.27 ± 0.15) than quercetin (log IC₅₀ = 4.56 ± 0.15). In conclusion, quercetin and its metabolites showed vasodilator effects with selectivity toward the resistance vessels. These effects are not due to or modulated by endothelial factors and are unrelated to changes in cytosolic Ca²⁺.