Background:
We previously have proved that sodium tanshinone II-A sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), is an opener and vasodilator of BKCachannel in the vascular smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca2+dynamics and activation of BKCachannel may not be the sole mechanism for the relaxation of the vascular tension by DS-201. Therefore, we hypothesized that the vasorelaxing effect of DS-20 may be also related to Ca2+channel and cytoplasmic Ca2+level in the VSMCs.Methods:Arterial tension was measured by Danish Myo Technology (DMT) myograph system in the mesentery vessels of rats, intracellular Ca2+level by fluorescence imaging system in the VSMCs of rats, and L-type Ca2+current by patch clamp technique in Ca2+channels transfected human embryonic kidney 293 (HEK-293) cells.Results:DS-201 relaxed the endothelium-denuded artery rings pre-constricted with PE or high K+and the vasorelaxation was reversible. Blockade of K+channel did not totally block the effect of DS-201 on vasorelaxation. DS-201 suppressed [Ca2+]itransient induced by high K+in a concentration-dependent manner in the VSMCs, including the amplitude of Ca2+transient, the time for Ca2+transient reaching to the [Ca2+]ipeak and the time to remove Ca2+from the cytoplasm. DS-201 inhibited L-type Ca2+channel with an EC50of 59.5 μM and at about 40% efficacy of inhibition. However, DS-201did not significantly affect the kinetics of Ca2+channel. The effect of DS-201 on L-type Ca2+channel was rate-independent.Conclusion:The effect of DS-201 on vasorelaxation was not only via activating BKCachannel, but also blocking Ca2+channel and inhibiting Ca2+influx in the VSMCs of rats. The results favor the use of DS-201 and Danshen in the treatment of cardiovascular diseases clinically.