The effects of quercetin were studied on contractile responses induced by noradrenaline, high KCl, Ca2+ and phorbol 12-myristate,13-acetate in rat aortic strips and on spontaneous mechanical activity in rat portal vein segments. Quercetin, 10(-6)-10(-4) M, inhibited in a concentration-dependent manner the contractions induced by noradrenaline, high KCl and Ca2+, this effect being observed when the drug was added before or after the induced contractions. The spontaneous myogenic portal activity was also inhibited. Mechanical removal of endothelium did not affect the relaxant effects of quercetin on noradrenaline-induced contractions. In addition, at the same range of concentrations, quercetin also relaxed the contractions induced by phorbol 12-myristate,13-acetate. Quercetin1 10(-5) and 5 x 10(-5) M, increased the aortic cyclic AMP content. However, pretreatment with 10(-7) M isoprenaline did not modify the relaxant effects of quercetin on noradrenaline-induced contractions and quercetin did not modify the relaxant effects of forskolin, which suggested that the vasodilator effects of quercetin were not mediated by inhibition of cyclic AMP phosphodiesterases. In conclusion, in isolated rat aorta quercetin produced a vasodilator effect that seems to be mainly related to the inhibition of protein kinase C. However, and since this drug exerts multiple biochemical effects, inhibition of other transduction pathways may be involved in this effect.