Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 23
Involvement of hydrogen peroxide in the activation of BKCa currents and vasodilator
effects of quercetin in rat coronary arteries
Giovanna Frazziano, Angel Cogolludo, Laura Moreno, Ana Briones, Federica Lodi,
Laura Cobeño, Mercedes Salaices, Juan Tamargo, and Francisco Perez-Vizcaino.
Department Pharmacology. School Medicine. Universidad Complutense de Madrid.
28040 Madrid. SPAIN. E-mail: frazzygio@jumpy.it
Calcium-activated potassium channels (BKCa) regulate coronary artery tone in vivo, play a
key role in blood pressure regulation and have been suggested as novel potential drug targets
in hypertension. The dietary flavonoid quercetin exerts systemic and coronary vasodilator
effects in vitro, reduces blood pressure in several rat models of hypertension and its
consumption is associated with a lower mortality rate from coronary heart disease in
epidemiological studies. We hypothesized that quercetin might activate BKCa channel in
isolated myocytes from rat coronary arteries and that this mechanism might be involved in its
coronary artery relaxant effects. Membrane currents were measured using the whole-cell
configuration of the patch-clamp technique. Quercetin (1-30 microM) increased the outward
currents in the whole range of test potentials and increased the frequency of spontaneous
transient outward currents (STOCs) carried by BKCa channels. These effects were abolished
by the selective BKCa blocker iberiotoxin and by the hydrogen peroxide scavenger catalase in
the internal pipette solution. The membrane permeable hydroperoxide t-butyl hydroperoxide
also increased outward currents. Quercetin increased dichlorofluorescein fluorescence, a
widely used indicator of intracellular hydrogen peroxide, in coronary arteries with a similar
magnitude and time-course than t-butyl hydroperoxide. Quercetin-induced increase was
prevented by polyethylenglycol-catalase, indicating the role of cytosolic hydrogen peroxide.
The vasodilator effect of low concentrations of quercetin in isolated rat coronary arteries was
inhibited by iberiotoxin. In conclusion, quercetin increased BKCa currents via production of
intracellular hydrogen peroxide. This effect is involved, at least partly, in the coronary
vasodilator effects of quercetin.
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