Daidzein relaxes rat cerebral basilar artery via activation of large-conductance Ca2+-activated K+ channels in vascular smooth muscle cells

Daidzein, a phytoestrogen, has been reported to produce vasodilation via inhibition of Ca2+ inflow. However, the involvement of large-conductance Ca2+-activated K+ (BKCa) channels in the effect of daidzein is debated. Therefore, the present study was designed to investigate the effect of daidzein on the rat cerebral basilar artery and the underlying molecular mechanisms. Isolated cerebral basilar artery rings and single vascular smooth muscle cells (VSMCs) were used for vascular reactivity and electrophysiology measurements, to investigate the effect of daidzein on BKCa channels in cerebral basilar artery smooth muscle. In addition, the human BKCa channel α-subunit gene (hslo) was transfected into HEK293 cells, to directly assess whether daidzein activates BKCa channels. The results showed that daidzein produced a concentration-dependent but endothelium-independent relaxation in rat cerebral basilar arteries. Paxilline, a selective BKCa channel blocker, significantly inhibited the daidzein-induced vasodilation, whereas NS1619, a selective BKCa channel opener, enhanced the vasodilation. In the whole-cell configuration, daidzein increased noisy oscillation currents in cerebral basilar artery VSMCs in a concentration-dependent manner, and washout of daidzein or blockade of BKCa channels with paxilline fully reversed the increase. However, daidzein did not substantially affect hSlo currents in HEK293 cells when applied to the outside of the cell membrane. In conclusion, these results indicate that the activation of BKCa channels in VSMCs at least partly contributes to the daidzein-induced vasodilation of the rat cerebral basilar artery. The β1-subunit of BKCa channels plays a critical role in the activation of BKCa currents by daidzein.