title: 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 microM 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; IC50 values were 930.3+/-133.5 microg/ml and 71.5+/-11.0 microg/ml. Removal of the endothelium did not significantly affect their vasodilator potencies; IC50 values were 842.1+/-123.8 microg/ml and 84.8+/-8.8 microg/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 Ca2+ channels was investigated in artery rings incubated with Ca2+-free buffer and primed with 1 microM 5-HT or 60 mM KCl for 5 min prior to addition of CaCl2 to elicit contraction. In 5-HT-primed preparations, the CaCl2-induced vasoconstriction was abolished by 2 mg/ml danshen aqueous extract and 200 microg/ml danshensu, whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract and 600 microg/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 Ca2+ 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. FrancisLam@cuhk.edu.hk
authors.forename: Francis Fu Yuen
authors.initials: FF
authors.lastname: Lam
authors.forename: John Hok Keung
authors.initials: JH
authors.lastname: Yeung
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Chan
authors.forename: Penelope Mei Yu
authors.initials: PM
authors.lastname: Or
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D007773:Lactates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C028972:dan-shen root extract; C035055:3,4-dihydroxyphenyllactic acid; D019789:Tetraethylammonium; D002118:Calcium