title: Mechanisms of the dilator action of cryptotanshinone on rat coronary artery.
abstract: In this study, we have investigated the actions of cryptotanshinone, an active, lipophilic 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 ethanol-extractable fraction of the herb. Extraction of the ethanol-soluble fraction from danshen provided a yield of 1%. The amount of cryptotanshinone determined in this ethanol extract was 3.682%, and it was 6 times more potent than the extract in relaxing 5-HT-precontracted coronary artery rings; IC(50) values were 2.65+/-0.15 microg/ml and 15.82+/-1.07 microg/ml, respectively. Involvement of endothelium-dependant mechanisms in their dilator effects were investigated by pretreatment of the artery rings with a cyclooxygenase inhibitor flurbiprofen (10 microM), a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), a muscarinic receptor antagonist atropine (100 nM), and by mechanical removal of the endothelium; none of these procedures produced a significant change on their dilator actions. Involvement of endothelium-independent mechanisms was investigated in endothelium-denuded artery rings pretreated with a beta-adrenoceptor antagonist propranolol (100 nM), an adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100 microM), a guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), and a potassium channel inhibitor tetraethylammonium (TEA, 100 mM); these also produced no change on their dilator actions. 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 for 5 min prior to adding CaCl(2) to elicit contraction. The danshen ethanol extract (100 microg/ml) abolished the CaCl(2)-induced vasoconstriction, whereas, cryptotanshinone (30 microg/ml) produced 59% inhibition. These findings suggest their vasorelaxant effects are independent of pathways mediated by the endothelium, muscarinic receptors, beta-adrenoceptors, adenylyl cyclase, and guanylyl cyclase, whereas, inhibition of Ca(2+) influx in the vascular smooth muscle cells is important for their vasodilator actions. The high vasodilator potency and the quantity of salvianolic acid B contained in danshen ethanolic extract suggest it is an important 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: Kam M
authors.initials: KM
authors.lastname: Chan
authors.forename: Penelope M Y
authors.initials: PM
authors.lastname: Or
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000032:analysis; D020013:Calcium Signaling / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010616:Phenanthrenes / Q000032:analysis / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*; D053630:Depsides
chemical_list: D000262:Adenylyl Cyclases; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D000431:Ethanol; D006162:Guanylate Cyclase; D019001:Nitric Oxide Synthase; D010616:Phenanthrenes; D011188:Potassium; D011451:Prostaglandin-Endoperoxide Synthases; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D012701:Serotonin; D012997:Solvents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C037886:cryptotanshinone; C076944:salvianolic acid B; D053630:Depsides