title: Salvianolic acid B, an aqueous component of danshen (Salvia miltiorrhiza), relaxes rat coronary artery by inhibition of calcium channels.
abstract: In this study, we have investigated the mechanism of action through which salvianolic acid, a constituent of the medicinal herb danshen (Salvia miltiorrhiza), causes relaxation of isolated coronary artery rings precontracted with 1 microM 5-hydroxytryptamine (5-HT). The vasorelaxant effects of salvianolic acid B were also compared with the aqueous extract of danshen. Extraction of the water-soluble fraction from danshen provided a yield of 17.5%. The amount of salvianolic acid B determined in this aqueous extract was 3.9%, and the extract was 6.3 times less potent than salvianolic acid B in relaxing 5-HT-precontracted coronary artery rings; IC(50) values were 930.3+/-133.5 microg/ml and 147.9+/-17.4 microg/ml, respectively. Removal of the endothelium did not significantly affect their vasodilator potencies; IC(50) values were 842.1+/-123.8 mictog/ml and 160.3+/-25.9 microg/ml. On the other hand, a potassium channel inhibitor tetraethylammonium (TEA, 10 mM) shifted their concentration-response curves by 1.7 and 2.9 folds. The possible involvement of Ca(2+) channels was investigated in artery rings incubated with Ca(2+)-free buffer and primed with 1 microM 5-HT or 60 mM KCl for 5 min prior to adding CaCl(2) to elicit contraction. In 5-HT-primed preparations, 2 mg/ml danshen aqueous extract and 0.72 mg/ml salvianolic acid B abolished the CaCl(2)-induced vasoconstriction, whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract and 1.44 mg/ml salvianolic acid B produced 90% inhibition. These findings suggest the vasorelaxant effects of danshen aqueous extract and salvianolic acid B were produced by inhibition of Ca(2+) influx in the vascular smooth muscle cells. The opening of K(+) channels had a minor contribution to their effects, but endothelium-dependent mechanisms were not involved. The high vasodilator potency and the quantity of salvianolic acid B contained in danshen aqueous extract suggest it is an important vasodilator constituent in this medicinal herb.
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 F Y
authors.initials: FF
authors.lastname: Lam
authors.forename: John H K
authors.initials: JH
authors.lastname: Yeung
authors.forename: Yiu W
authors.initials: YW
authors.lastname: Kwan
authors.forename: Kam M
authors.initials: KM
authors.lastname: Chan
authors.forename: Penelope M Y
authors.initials: PM
authors.lastname: Or
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027544:Salvia / Q000737:chemistry*; D012701:Serotonin / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D053630:Depsides
chemical_list: D001572:Benzofurans; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009543:Nifedipine; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D012701:Serotonin; D019789:Tetraethylammonium; C076944:salvianolic acid B; D053630:Depsides