InKyeom Kim

Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea

Abstract:

It is of interest to investigate whether synthetic thioflavonoids have vasorelaxant actions as natural flavonoids. We tested the hypothesis that 3’,4’-dimethoxythioflavone induces endothelium-dependent vasorelaxation through activation of epidermal growth factor (EGF) receptor.

Rat aortic rings were mounted in organ baths, and subjected to relaxation upon contraction. 3’,4’-dimethoxythioflavone induced endothelium-dependent vasorelaxation, which was attenuated by pretreatment with either L-Nω-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, or 1H-​[1,​2,​4]oxadiazolo[4,​3-​a]quinoxalin-​1-​one (ODQ), an inhibitor of soluble guanylate cyclase. 3’,4’-Dimethoxythioflavone -induced vasorelaxation was not affected by pretreatment with a general estrogen receptor antagonist ICI 182,780, a selective estrogen receptor-α antagonist methyl-piperidino-pyrazole dihydrochloride (MPP), or a G-protein coupled receptor 30 antagonist G15. However, pretreatment with EGF receptor blockers AG1478 or DAPH, but not with a phosphatidylinositol-3 kinase inhibitor LY294002 or an Akt1/2 kinase inhibitor Akt Inhibitor VIII, attenuated 3’,4’-dimethoxythioflavone -induced vasorelaxation. In addition, pretreatment with a Src inhibitor PP2 or an ERK inhibitor U0126 also attenuated vascular relaxation induced by cumulative addition of 3’,4’-dimethoxythioflavone. However, neither a mitochondrial electron transport inhibitor rotenone, an NADPH oxidase inhibitor apocynin, nor a superoxide dismutase mimetic MnTMPyP affected the vascular relaxation induced by cumulative addition of 3’,4’-dimethoxythioflavone.

In conclusion, 3’,4’-dimethoxythioflavone induces endothelium-dependent vasorelaxation through activation of EGF receptor and Src/ERK pathway in rat aorta.

Keywords: 3’,4’-dimethoxythioflavone, endothelium-dependent vasorelaxation, EGF receptor and Src/ERK pathway.