Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels

被引:129
作者
Calderone, V [1 ]
Chericoni, S
Martinelli, C
Testai, L
Nardi, A
Morelli, I
Breschi, MC
Martinotti, E
机构
[1] Univ Pisa, Dipartimento Psichiatria Neurobiol Farmacol & Bio, Via Bonanno 6, I-56126 Pisa, Italy
[2] Univ Pisa, Dipartimento Chim Bioorgan & Biofarm, I-56126 Pisa, Italy
[3] Univ Pisa, Dipartimento Sci Farmaceut, I-56126 Pisa, Italy
关键词
flavonoid; flavone; flavanone; calcium-activated potassium channel; ATP-sensitive potassium channel; vasorelaxing effect;
D O I
10.1007/s00210-004-0964-z
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A flavonoid-rich diet has been associated with a lower incidence of cardiovascular diseases, probably because of the antioxidant and vasoactive properties of flavonoids. Indeed, many flavonoids show vasorelaxing properties, due to different and often not yet completely clarified mechanisms of action. Among them, the activation of vascular potassium channels has been indicated as a possible pathway, accounting, at least in part, for the vasodilatory action of some flavonoid derivatives, such as apigenin and dioclein. Therefore, this work aims at evaluating, on in vitro isolated rat aortic rings, the endothelium-independent vasorelaxing effects of a number of flavonoid derivatives, to identify a possible activation of calcium-activated and/or ATP-sensitive potassium channels and to indicate some possible structure-activity relationships. Among the several flavonoids submitted to the pharmacological assay, only baicalein and quercetagetin were almost completely ineffective, while quercetin, hesperidin, quercitrin and rhoifolin exhibited only a partial vasorelaxing effect. On the contrary, acacetin, apigenin, chrysin, hesperetin, luteolin, pinocembrin, 4'-hydroxyflavanone, 5-hydroxyflavone, 5-methoxyflavone, 6-hydroxyflavanone and 7-hydroxyflavone, belonging to the chemical classes of flavones and flavanones, showed full vasorelaxing effects. The vasodilatory activity of hesperetin, luteolin, 5-hydroxyflavone and 7-hydroxyflavone were antagonised by tetraethylammonium chloride, indicating the possible involvement of calcium-activated potassium channels. Moreover, iberiotoxin clearly antagonised the effects of 5-hydroxyflavone, indicating the probable importance of a structural requirement (the hydroxy group in position 5) for a possible interaction with large-conductance, calcium-activated potassium channels. Finally, glibenclamide inhibited the vasorelaxing action of luteolin and 5-hydroxyflavone, suggesting that ATP-sensitive potassium channels may also be involved in their mechanism of action.
引用
收藏
页码:290 / 298
页数:9
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