Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels

Abstract

In this study, we have investigated the actions of danshensu, an active, water-extractable component of the medicinal herb danshen ( Salvia miltiorrhiza), on rat isolated coronary artery rings precontracted with 1 μM 5-hydroxytryptamine (5-HT) and its action compared to the water-extractable fraction of the herb. Extraction of the water-soluble fraction from danshen ( S. miltiorrhiza) provided yield of 17.5% (35 g/200 g). The amount of danshensu determined in the crude danshen herb and in its aqueous fraction was 0.45 mg/g (0.045%) and 3.28 mg/g (0.33%). The danshen aqueous extract was 13 times less potent than danshensu in relaxing 5-HT-precontracted coronary artery rings; IC 50 values were 930.3 ± 133.5 μg/ml and 71.5 ± 11.0 μg/ml. Removal of the endothelium did not significantly affect their vasodilator potencies; IC 50 values were 842.1 ± 123.8 μg/ml and 84.8 ± 8.8 μg/ml. On the other hand, a potassium channel inhibitor tetraethylammonium (TEA, 10 mM) shifted their concentration–response curves by 1.7 and 2.2 folds. The possible involvement of Ca 2+ channels was investigated in artery rings incubated with Ca 2+-free buffer and primed with 1 μM 5-HT or 60 mM KCl for 5 min prior to addition of CaCl 2 to elicit contraction. In 5-HT-primed preparations, the CaCl 2-induced vasoconstriction was abolished by 2 mg/ml danshen aqueous extract and 200 μg/ml danshensu, whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract and 600 μg/ml danshensu were required to abrogate the vasoconstriction. These findings suggest the vasorelaxant actions of danshen aqueous extract and danshensu were produced by inhibition of Ca 2+ influx in the vascular smooth muscle cells. The opening of K + channels had a minor contribution to the response, but endothelium-dependent mechanisms were not involved.