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

Abstract

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.

Evaluation of the Intravenous and Topical Routes for Ocular Delivery of Hesperidin and Hesperetin

“…2 Additionally, these compounds have been demonstrated to be effective in the treatment of chronic venous insufficiency. 3,4 Reports also suggest that hesperidin can prevent microvascular leakage through their capillary wall-strengthening action: hesperidin methyl chalcone, given intravenously, significantly inhibited the macromolecular permeability-increasing effect of bradykinin, LTB4, and histamine. 5 Furthermore, hesperidin and hesperitin can reduce platelet aggregation, a factor involved in the blockage of retinal blood vessels.…”

Mechanism of Flavonoids Action in Smooth Muscle Relaxation

“…Apigenin on isolated aortic rings [132][133][134] ; apigenin induced vasodilation is blocked by L-NAME.…”

Different mechanisms of actions of genistein and quercetin on spontaneous contractions of rabbit duodenum

“…It has also been described that flavonoids have vasorelaxing effects in isolated rat aortic rings (15,16). Genistein and quercetin produce a concentration-dependent relaxation on the gastric tone in mouse isolated stomach and inhibit intestinal peristalsis in guinea pig (5,7).…”