Abstract
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 BK(Ca) channel in the vascular smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca(2+) dynamics and activation of BK(Ca) channel 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 Ca(2+) channel and cytoplasmic Ca(2+) level in the VSMCs. Methods: Arterial tension was measured by Danish Myo Technology (DMT) myograph system in the mesentery vessels of rats, intracellular Ca(2+) level by fluorescence imaging system in the VSMCs of rats, and L-type Ca(2+) current by patch clamp technique in Ca(2+) 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 [Ca(2+)](i) transient induced by high K(+) in a concentration-dependent manner in the VSMCs, including the amplitude of Ca(2+) transient, the time for Ca(2+) transient reaching to the [Ca(2+)](i) peak and the time to remove Ca(2+) from the cytoplasm. DS-201 inhibited L-type Ca(2+) channel with an EC(50) of 59.5 μM and at about 40% efficacy of inhibition. However, DS-201did not significantly affect the kinetics of Ca(2+) channel. The effect of DS-201 on L-type Ca(2+) channel was rate-independent. Conclusion: The effect of DS-201 on vasorelaxation was not only via activating BK(Ca) channel, but also blocking Ca(2+) channel and inhibiting Ca(2+) influx in the VSMCs of rats. The results favor the use of DS-201 and Danshen in the treatment of cardiovascular diseases clinically.