Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we...Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China(Nos.30960450,81173110)Yunnan Provincial Science and Technology Department(Nos.2011FA 022,2012BC012,2014FA010,2014FB037,2014BC012)
文摘Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.
