Dual effect of quercetin on rat isolated portal vein smooth muscle contractility

This study examined the effects of quercetin on spontaneously contracting portal veins isolated from healthy young adult male and female Wistar rats (250-300 g). Quercetin (10(-7)-10(-4) M) always produced significant biphasic effects, comprising an initial brief stimulant effect (rise in basal tone), followed by a sustained, longer-lasting secondary relaxant (inhibitory) effect on the venous tissues. The initial brief contractions of the venous muscle preparations were not modified by preincubation of the tissues with prazosin (10(-6) M), suggesting that the initial upsurge in basal tone and increases in contractile frequencies of the venous tissues were probably not mediated via alpha1-adrenoceptor stimulation. However, preincubation of the tissues with nifedipine (10(-7) M) significantly suppressed (p < 0.05) or attenuated the initial stimulant effect of quercetin, suggesting that the flavonoid might be activating L-type voltage-dependent calcium channels. The vasorelaxant effect of quercetin was partially but not significantly (p > 0.05) inhibited by L-NAME (100 microM) or indomethacin (10 microM), suggesting that the vasorelaxant effect of the flavonoid was unlikely to be mediated via endothelium-dependent relaxing factor (EDRF), or through prostacyclin (PGI(2)) pathways. N-p-tosyl-l-phenylalanine-chloromethyl-ketone (TPCK, 3 microM) significantly (p < 0.01) antagonised quercetin-induced relaxations, suggesting that cAMP-dependent protein kinases might have contributed, at least in part, towards the vasorelaxant effect of quercetin on rat isolated portal veins.