Dihydrotanshinone, a lipophilic component of Salvia miltiorrhiza (danshen), relaxes rat coronary artery by inhibition of calcium channels

Aim of the study: Dihydrotanshinone is a lipophilic component of the medicinal herb Salvia miltiorrhiza (danshen) belonging to the family of Labiatae. In this study, we have investigated the mechanisms of its relaxant effect on rat-isolated coronary artery. Materials and Methods: Rat coronary artery rings were precontracted with 1 mu M 5-hydroxytryptamine (5-HT). Involvement of endothelium-dependant mechanisms were investigated by pretreatment of the artery rings with a cyclooxygenase inhibitor flurbiprofen (10 mu M), a nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M), a muscarinic receptor antagonist atropine (100 nM), and by mechanical removal of the endothelium. 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-puririe-6-amine (SQ22536, 100 mu M), a guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ 10 mu M), and a potassium channel inhibitor tetraethylammonium (TEA, 10 mM). Involvement of Ca2+ channels was investigated in artery rings incubated with Ca2+-free buffer and primed with 1 mu M 5-HT for 5 min prior to adding CaCl2 to elicit contraction. Results: Dihydrotanshinone relaxed the 5-HT-precontracted coronary artery rings with an IC50 value of 10.39 +/- 1.69 mu M. None of the above inhibitors or antagonists tested produced a significant change on the vasorelaxant effect of dihydrotanshinone, except ODQ caused a 50% reduction. Pre-incubation of the artery rings for 10 min with dihydrotanshinone (100 mu M) abolished the CaCl2-induced vasoconstriction. Conclusions: These findings suggest that inhibition of Ca2+ influx in the vascular smooth muscle cells is important for the vasorelaxant effect of dihydrotanshinone, and it is independent of pathways involving the endothelium, muscarinic receptors, beta-adrenoceptors, adenylyl cyclase, and guanylyl cyclase. (C) 2008 Elsevier Ireland Ltd. All rights reserved.