title: Scutellarin attenuates endothelium-dependent aasodilation impairment induced by hypoxia reoxygenation, through regulating the PKG signaling pathway in rat coronary artery.
abstract: 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 (cGMP) 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-cGMPS (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.
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Zhou
authors.affiliation: Zhaotong Institute of Tianma, Zhaotong 657000, China.
authors.forename: Xian-Lun
authors.initials: XL
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qing
authors.affiliation: Department of Periodontology and Implant Dentistry, The First People's Hospital of Yun-Nan Province, Kunhua Hospital Affiliated to Kunming University of Science and Technology, Kunming 650032, China. Electronic address: liuyingting999@163.com.
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. Electronic address: ywmbessie@yeah.net.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Yang
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000187:drug effects; D015687:Cell Hypoxia; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases; D005965:Glucuronates / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013873:Thionucleotides / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D005965:Glucuronates; D008840:Microfilament Proteins; D010750:Phosphoproteins; D013873:Thionucleotides; D000098662:Vasodilator-Stimulated Phosphoprotein; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C484876:scutellarin; D047310:Apigenin; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester
keywords: Coronary artery; Endothelium-dependent vasodilation; Hypoxia reoxygenation; Rat; Scutellarin; cGMP-dependent protein kinase