Possible Involvement of Ca2+ Activated K+ Channels, SK Channel, in the Quercetin-Induced Vasodilatation

Abstract

Effects of quercetin, a kind of flavonoids, on the vasodilating actions were investigated. Among the mechanisms for quercetin-induced vasodilatation in rat aorta, the involvement with the Ca 2＋ activated K ＋ (KCa) channel was examined. Pretreatment with NE (5 μM) or KCl (60 mM) was carried out and then, the modulation by quercetin of the constriction was examined using rat aorta ring strips (3 mm) at 36.5 o C. Quercetin (0.1 to 100 μM) relaxed the NE-induced vasoconstrictions in a concentrationdependent manner. NO synthesis (NOS) inhibitor, NG-monomethyl-L-arginine acetate (L-NMMA), at 100 μM reduced the quercetin (100 μM)-induced vasodilatation from 97.8±3.7% (n=10) to 78.0±11.6 % (n=5, p＜ 0.05). Another NOS inhibitor, L-NG-nitro arginine methyl ester (L-NAME), at 100 μM also had the similar effect. In the presence of both 100 μM L-NMMA and 10 μM indomethacin, the quercetin-induced vasodilatation was further attenuated by 100 μM tetraethylammonium (TEA, a KCa channel inhibitor). Also TEA decreased the quercetin-induced vasodilatation in endothelium-denuded rat aorta. Used other KCa channel inhibitors, the quercetin-induced vasodilatation was attenuated by 0.3 μM apamin (a SK channel inhibitor), but not by 30 nM charybdotoxin (a BK and IK channel inhibitor). Quercetin caused a concentration-dependent vasodilatation, due to the endotheliumdependent and -independent actions. Also quercetin contributes to the vasodilatation selectively with SK channel on smooth muscle.

Relaxant and Antioxidant Capacity of the Red Wine Polyphenols, Resveratrol and Quercetin, on Isolated Mice Corpora Cavernosa

“…The main finding of this study is twofold: (i) resveratrol, but not quercetin, relaxes isolated mice CC in a concentration-dependent manner through mechanisms independent of NO/sGC; and (ii) resveratrol is more potent than quercetin in reversing PA-induced decrease in nNOS responses. As resveratrol and quercetin are believed to contribute to the cardiovascular benefits of moderate red wine consumption, numerous studies have shown that both polyphenols can induce vasorelaxation [3][4][5][6][7][8][9][10]. Even in corporal tissues, positive effects to resveratrol and quercetin administration have been reported [24][25][26][27][28][29].…”

“…All experiments were performed on adult (8)(9)(10)(11)(12) weeks) male Swiss mice (n = 143), obtained from Janvier (Saint-Berthevin, France) or on 129SvEvS7 sGC wild type (n = 15, sGCα 1 +/+ ) or sGC alpha 1 knockout (n = 15, sGCα 1 −/− ) mice. These 129SvEvS7 mice were bred in the SPF facility of the Inflammation Research Center, VIB, Ghent, Belgium [21].…”

“…Both resveratrol and quercetin are known to relax arteries in different vascular beds, mainly by activation of the nitric oxide (NO)/ soluble guanylyl cyclase (sGC) pathway [3][4][5][6][7]. However, some part of the relaxation induced by these polyphenols occurs NO/sGC-independent through activation of different types of K + channels [7][8][9][10]. Several studies showed that, besides their vasorelaxant effect, resveratrol and quercetin can reduce oxidative stress [11][12][13][14][15][16][17].…”

Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca2+-activated K+Channels

“…-activated K (KCa) channels [18,19], voltage-dependent K (KV) channels [20], CFTR (cystic fibrosis transmembrane regulator) chloride channels [21], and neurotransmitter-induced current [22]. Among these paths, the large conductance Ca 2＋ -activated K ＋ (BKCa) channel has been theorized as having relevance to cell proliferation, but this assumption is still controversial [23][24][25][26][27].…”

Qualitative and Quantitative Analysis of Five Bioactive Flavonoids in <i>Salix bordensis</i> Turcz. by HPLC-DAD and HPLC-ESI-MS

“…For example, kaempferol shows an anti-inflammatory effect on activated macrophages [3], has chemopreventive properties in brain tumors [4], and has an suppression effect on cell proliferation in human gut cancer lines [5] [6]. Similarly, quercetin also has various pharmacological actions, including scavenging of free radicals [7]- [9], modulation of epoxyeicosanoic acid synthesis, prevention of platelet aggregation [8], and vasodilating effects [10] [11].…”