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: Ya-Juan Chen, Lei Wang, Guang-Yu Zhou, Xian-Lun Yu, Yong-Hui Zhang, Na Hu, Qing-Qing Li, Chen Chen, Chen Qing, Ying-Ting Liu, Wei-Min Yang
• Journal: Chinese journal of natural medicines (Chin J Nat Med) Vol. 13 Issue 4 Pg. 264-73 (Apr 2015) ISSN: 1875-5364 [Electronic] China
• PMID: 25908623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cell Adhesion Molecules
• Glucuronates
• Microfilament Proteins
• Phosphoproteins
• Thionucleotides
• vasodilator-stimulated phosphoprotein
• 8-bromoguanosino-3',5'-cyclic monophosphorothioate
• scutellarin
• Apigenin
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP
• NG-Nitroarginine Methyl Ester

Topics

• 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)