Scutellarin attenuates endothelium-dependent aasodilation impairment induced by hypoxia reoxygenation, through regulating the PKG signaling pathway in rat coronary artery.
10.1016/S1875-5364(15)30013-3
- Author:
Ya-Juan CHEN
1
;
Lei WANG
1
;
Guang-Yu ZHOU
1
;
Xian-Lun YU
2
;
Yong-Hui ZHANG
1
;
Na HU
1
;
Qing-Qing LI
1
;
Chen CHEN
1
;
Chen QING
1
;
Ying-Ting LIU
3
;
Wei-Min YANG
4
Author Information
1. School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
2. Zhaotong Institute of Tianma, Zhaotong 657000, China.
3. 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.
4. School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. Electronic address: ywmbessie@yeah.net.
- Publication Type:Journal Article
- Keywords:
Coronary artery;
Endothelium-dependent vasodilation;
Hypoxia reoxygenation;
Rat;
Scutellarin;
cGMP-dependent protein kinase
- MeSH:
Animals;
Apigenin;
pharmacology;
Cell Adhesion Molecules;
drug effects;
Cell Hypoxia;
Coronary Vessels;
drug effects;
Cyclic GMP;
analogs & derivatives;
metabolism;
pharmacology;
Cyclic GMP-Dependent Protein Kinases;
Glucuronates;
pharmacology;
Microfilament Proteins;
drug effects;
NG-Nitroarginine Methyl Ester;
metabolism;
pharmacology;
Phosphoproteins;
drug effects;
Rats;
Rats, Sprague-Dawley;
Reperfusion Injury;
complications;
physiopathology;
Signal Transduction;
drug effects;
Thionucleotides;
metabolism;
pharmacology;
Vasodilation;
drug effects;
physiology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2015;13(4):264-273
- CountryChina
- Language:English
-
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.
