3',4'-Dimethoxythioflavone induces endothelium-dependent vasorelaxation through activation of epidermal growth factor receptor. |
Authors: |
Jang, EJ Seok, YM Lee, JI Cho, HM Sohn, UD Kim, IK
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Citation: |
Jang EJ, etal., Naunyn Schmiedebergs Arch Pharmacol. 2012 Dec 12. |
RGD ID: |
7205478 |
Pubmed: |
PMID:23232926 (View Abstract at PubMed) |
DOI: |
DOI:10.1007/s00210-012-0818-z (Journal Full-text) |
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-N (omega)-nitroarginine methyl ester, an inhibitor of nitric oxide synthase, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, 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-alpha antagonist methyl-piperidino-pyrazole dihydrochloride, 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 the 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 the 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.
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