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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 BKCa channel in the vascular smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca2+dynamics and activation of BKCa 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 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+]i transient 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+]i peak and the time to remove Ca2+ from the cytoplasm. DS-201 inhibited L-type Ca2+ channel with an EC50 of 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 BKCa channel, 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. [ABSTRACT FROM AUTHOR]

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.

Chronic hypertension is associated with an impaired vascular relaxation caused by an increased vascular tone; however, the underlying mechanisms are not fully understood in human patients. The present study was to investigate whether large-conductance Ca(2+)- and voltage-activated K(+) (BK(Ca)) channels are involved in dysfunctional relaxation of artery in Han Chinese patients with hypertension using the perforated patch clamp, inside-out single-channel, and macromembrane patch recording techniques to determine whole-cell current, spontaneous transient outward current, open probability, and Ca(2+) sensitivity and the reverse transcription polymerase chain reaction and Western blot analysis to examine the gene and protein expression of α-subunit (KCa1.1) and β1-subunit (KCNMB1) of BK(Ca) channels in isolated human vascular smooth muscle cells and mesenteric arteries from normotensive and hypertensive patients. It was found that whole-cell current density, spontaneous transient outward current, and Ca(2+) sensitivity, but not single-channel open probability and slope conductance, were significantly decreased in vascular smooth muscle cells from patients with hypertension. Interestingly, mRNA and protein levels of KCNMB1, but not KCa1.1, were reduced in the arterial tissue from patients with hypertension. These results demonstrate for the first time that whole-cell current, spontaneous transient outward current, and Ca(2+) sensitivity of BK(Ca) channels are reduced in human vascular smooth muscle cells, which resulted from downregulation of β1-subunit of the channel. This may account, at least in part, for the dysfunction of artery relaxation in Han Chinese patients with primary hypertension.