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

SUMMARY: 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 alpha(1)-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 μM) or indomethacin (10 μM), 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 μM) 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.