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Rivista di Angiologia
Official Journal of the , the International Union of Phlebology and the
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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International Angiology 2012 December;31(6):557-64
Mechanisms that underlie the induction of vasodilation in pulmonary artery by rutin
Li Q. 1, Niu S. 1, Wang R. 1, Li Y. 1, Zhang R. 1, Zhu D. 1, 2, 3
1 Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China;
2 Biopharmaceutical Key Laboratory, of Heilongjiang Province, Harbin, China;
3 Biopharmaceutical Key Laboratory of Ministry of Education, China
AIM: Rutin, also known as violaguercitrin, is a bioflavonoid and has a wide range of biological activity. However, the effect of this compound on arteries is not elucidated. Therefore, the objective of this study was to investigate the mechanism underling the induction of vasodilation in pulmonary artery (PA) by the natural product, rutin.
METHODS: Firstly, the isometric tension of the artery rings was studied in vitro with force-electricity transducers. In PA endothelium-intact (EI) rings, rutin elicited concentration-dependent relaxation after the PA rings were pre-contracted by phenylephrine (PE), but induced mesenteric artery (MA) vasoconstriction. Inhibited the endothelial nitric oxide synthase (eNOS) by NG-Nitro-L-arginine Methyl Ester (L-NAME) or removed the PA endothelium would decrease the relaxation effect of rutin.
RESULTS: The NO production was increased in rutin-treated bovine pulmonary artery endothelial cells (BPAECs) detected by fluorescent probe 4-amino-5-methylamino-2’,7’-difluorofluorescein diacetate (DAF-FM), which verify the functional study results. Moreover, western blot analysis revealed that rutin increased the phosphorylation of eNOS at Ser 1177, but decreased the phosphorylation of eNOS at Thr 495, and did not affect the overall expression of eNOS.
CONCLUSION: These results suggested that rutin-induced relaxation of PAs share NO-eNOS activation pathways, including phosphorylation of Ser 1177, and dephosphorylation at Thr 495. Rutin also has specific action because it exerts a vasodilator influence on the PAs but not MAs.