The Role of Potassium Channels in the Vasodilatation Induced by Resveratrol and Naringenin in Isolated Human Umbilical Vein.

Preclinical Research Potassium (K+ ) channels have a key role in the maintenance of smooth muscle tone; a variety of agonists can modify the tone by altering K+ -channel activity. The aim of this study was assess the effects of the phenols, resveratrol, and naringenin on K+ -channels of the vascular smooth muscle. Segments of human umbilical vein (HUV) without endothelium were precontracted using serotonin (100 µM) or 100 mM K+ to derive cumulative concentration-response curves using increasing concentrations of resveratrol or naringenin. K+ -channel inhibitors were added in the bath before resveratrol (1-100 µM) or naringenin (0.01-1 mM) in assess the role of K+ -channels in their effects on HUV precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM), a nonselective blocker of Ca2+ -dependent and inward rectifier K+ -channels (respectively) induced significant shifts to the right (P < 0.05) of resveratrol. concentration-response curves. The effect of naringenin was antagonized by 4-AP (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K+ -channels are probably involved in the resveratrol vasodilatatory effect, while naringenin seems to affect 4-AP-sensitive K+ -channels. However, other mechanisms of vasodilation induced by polyphenols could not be excluded. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.

The different effects of resveratrol and naringenin on isolated human umbilical vein: the role of ATP-sensitive K⁺ channels.

The blood flow from the placenta to the fetus depends on human umbilical vein (HUV) vascular tone. ATP-sensitive K(+) (K(ATP)) channels link the metabolic state of the cell to membrane potential, and their activation in the HUV represents protection against hypoxia. The aims of our study were to assess the effects of resveratrol and naringenin on the HUV and to define the roles of K(ATP) channels in their effects. Serotonin or 100 mM K(+) were used for precontraction of the HUV without endothelium. The cumulative concentration-response curves were obtained by adding increasing concentrations of resveratrol or naringenin. Glibenclamide was used, in order to test the role of K(ATP) channels in its effect. Resveratrol induced more potent vasodilatation of serotonin- and 100 mM K(+)-precontracted HUV than naringenin. Glibenclamide induced significant shift to the right of the concentration-response curves of resveratrol and P1075 (a specific opener of K(ATP) channels). Western blotting showed that HUV expressed protein Kir6.1. Thus, resveratrol and naringenin produce dilatation of HUV. It seems that K(ATP) channels are involved in the relaxation of HUV induced by resveratrol, while naringenin seems to interact with other ion channels. The K(+) channel-independent mechanism(s) of these polyphenols could not be excluded.