Epidemiological studies indicate that low incidence of cardiovascular disease is associated with dietary intake of polyphenolic compounds, which are abundantly present in fruits and vegetables. There is solid evidence that quercetin, a polyphenolic compound, exerts vasodilator effects in addition to its antioxidant activity. Therefore, in this study, the contribution of shear stress-induced nitric oxide to the vasodilator effect of quercetin in mesenteric bed was investigated. Dose-dependent vasodilator effects of quercetin on the perfusion pressure increased by phenylephrine were recorded in the presence of L-arginine/cGMP pathway inhibitors or superoxide dismutase in the perfused mesenteric vascular beds isolated from rats. Quercetin (1, 5 and 10 mu M) concentration-dependently decreased the perfusion pressure raised by phenylephrine (3-6 mu M) in the endothelium-intact mesenteric bed. The relaxations occured at 1 and 5 mu M quercetin were significantly inhibited by nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (L-NA, 100 mu M) or the guanylate cyclase inhibitor, 1H-[ 1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 mu M), while relaxations to 10 mu M quercetin were not affected. Removal of endothelium significantly reduced the relaxations at lower concentrations of quercetin but was without effect on relaxations induced by 10 mu M. Calmidazolium (0.5 mu M), a calmodulin inhibitor did not significantly affect the quercetin responses but a superoxide anion scavanger, superoxide dismutase (SOD, 100 U mL(-1)) significantly improved the quercetin-induced relaxations especially at 1 and 5 mu M. These findings suggest that quercetin induces endothelium-dependent vasodilatations at lower concentrations by increasing the bioactivity of sustained nitric oxide release evoked by perfusion pressure. However, the vasodilatations induced by high concentrations of quercetin are endothelium-independent.