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

Abstract

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 μM 5-hydroxytryptamine (5-HT). Involvement of endothelium-dependant mechanisms were investigated by pretreatment of the artery rings with a cyclooxygenase inhibitor flurbiprofen (10 μM), a nitric oxide synthase inhibitor N G-nitro-L-arginine methyl ester (L-NAME, 100 μM), 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 β-adrenoceptor antagonist propranolol (100 nM), an adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9 H-purine-6-amine (SQ22536, 100 μM), a guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,10 μM), and a potassium channel inhibitor tetraethylammonium (TEA, 10 mM). Involvement of Ca 2+ channels was investigated in artery rings incubated with Ca 2+-free buffer and primed with 1 μM 5-HT for 5 min prior to adding CaCl 2 to elicit contraction. Results Dihydrotanshinone relaxed the 5-HT-precontracted coronary artery rings with an IC50 value of 10.39 ± 1.69 μM. 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 μM) abolished the CaCl 2-induced vasoconstriction. Conclusions These findings suggest that inhibition of Ca 2+ 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, β-adrenoceptors, adenylyl cyclase, and guanylyl cyclase.