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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 Ca2+ 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°C. Quercetin (0.1 to 100 μM) relaxed the NE-induced vasoconstrictions in a concentration-dependent 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 endothelium-dependent and -independent actions. Also quercetin contributes to the vasodilatation selectively with SK channel on smooth muscle.
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Fig. 1.
Concentration-dependent vasodilatation by cumulative administrations of quercetin. Symbols used are control (open circles, n=10), pretreatment with L-NMMA (triangles, n=5), L-NMMA and indomethacin (squares, n=5). Values (%) are represented as mean±S.E.M. ∗p<0.05, ∗∗p<0.01, with respect to control value.
Fig. 2.
Modulation of L-NMMA and indomethacin resistant relaxation at 100 μM quercetin. The vasodilatation in the presence of L-NMMA and indomedhacin (n=5) means as control value in this graph. The vasodilatations by L-NMMA and indomethacin plus TEA (n=5), by L-NMMA and indomethacin plus apamin (n=5), and by L-NMMA and indomethacin plus charybdotoxin (n=5) were compared with that of L-NMMA and indomedhacin. Values (%) are represented as mean±S.E.M. ∗∗p<0.01, with respect to control value.
Fig. 3.
Modulation of quercetin (100 μM)-induced vasodilatation (n=10) in the removal of endothelium (n=5) and the removal of endothelium plus TEA (n=5). Values (%) are represented as mean± S.E.M. ∗p<0.05, with respect to control value.
Table 1.
Modulation of the quercetin-induced vasodilatation
| Quercetin (μM) | ||||||||
|---|---|---|---|---|---|---|---|---|
| N | 0.1 | 0.3 | 1 | 3 | 10 | 30 | 100 | |
| Control | 10 | 1.7±0.53 | 3.6±0.90a | 6.9±0.91a | 12.4±1.1b | 32.0±5.7c | 54.1±4.4c | 97.8±3.7c |
| L-NMMA 100 μM | 5 | 1.9±0.55 | 4.1±1.3 | 7.3±1.8 | 13.0±2.4 | 25.4±4.8 | 38.7±6.0x | 78.0±11.6x |
| L-NAME 100 μM | 5 | 1.2±0.89 | 3.0±1.1 | 7.0±2.0 | 13.2±3.7 | 21.1±4.6x | 33.0±5.3y | 69.5±6.1y |
| Endothelium-denuded | 5 | 1.8±0.55 | 3.8±1.6 | 8.5±1.9 | 13.0±2.6 | 30.8±4.9 | 44.2±4.2x | 77.9±2.4x |
Values (%) represent mean±S.E.M. a and x: p<0.05, b and y: p<0.01, c: p<0.001. Symbols of a, b, and c mean significant difference in comparison between effect of quercetin itself at each concentration and the maximal contraction induced by NE. Symbols of x and y mean significant difference as compared with control (quercetin alone).
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