Quercetin relaxes rat tail main artery partly via a PKG ‐mediated stimulation of K Ca 1.1 channels

Aim Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca 2+ ‐activated K + ( K Ca 1.1) channels. Thus, the aim of the present investigation was to address the hypothesis that quercetin‐induced vasorelaxation is caused by a PKG ‐mediated stimulation of K Ca 1.1 currents. Methods Single freshly isolated myocytes and endothelium‐denuded rings of the rat tail main artery were employed for electrophysiological and contractility measurements respectively. Results Quercetin relaxed vessels and increased K Ca 1.1 currents in a concentration‐dependent manner: both effects were antagonized by the specific K Ca 1.1 channel blocker iberiotoxin. Stimulation of K Ca 1.1 currents was fully reversible upon drug washout, markedly reduced by Rp‐8‐Br‐ PET ‐ cGMP s, a PKG ‐inhibitor, but not affected by catalase. Quercetin shifted by 34.3 mV the voltage dependence of K Ca 1.1 channel activation towards more negative membrane potentials without affecting its slope. Under conditions of tight functional coupling between sarcoplasmic reticulum Ca 2+ release sites and K Ca 1.1 channels, quercetin decreased both the frequency and the amplitude of K Ca 1.1 transient currents in a ryanodine‐like manner. Conclusion The natural flavonoid quercetin relaxes the rat tail main artery partly via a PKG ‐mediated stimulation of smooth muscle K C a 1.1 channels.