Li Q, Niu S, Wang R, Li Y, Zhang R, Zhu D
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, China.
Int Angiol. 2012 Dec;31(6):557-64.
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.
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.
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.
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.
芦丁，又称芸香苷，是一种生物类黄酮，具有广泛的生物活性。然而，该化合物对动脉的影响尚未阐明。因此，本研究的目的是探究天然产物芦丁诱导肺动脉（PA）血管舒张的机制。
首先，使用力电换能器在体外研究动脉环的等长张力。在PA内皮完整（EI）环中，用去氧肾上腺素（PE）预收缩PA环后，芦丁引起浓度依赖性舒张，但对肠系膜动脉（MA）有血管收缩作用。用NG-硝基-L-精氨酸甲酯（L-NAME）抑制内皮型一氧化氮合酶（eNOS）或去除PA内皮会降低芦丁的舒张作用。
用荧光探针4-氨基-5-甲基氨基-2'，7'-二氟荧光素二乙酸酯（DAF-FM）检测发现，经芦丁处理的牛肺动脉内皮细胞（BPAECs）中一氧化氮（NO）生成增加，这证实了功能研究结果。此外，蛋白质印迹分析显示，芦丁增加了eNOS在丝氨酸1177位点的磷酸化，但降低了eNOS在苏氨酸495位点的磷酸化，且不影响eNOS总体表达。
这些结果表明，芦丁诱导的PA舒张共享NO-eNOS激活途径，包括丝氨酸1177位点的磷酸化和苏氨酸495位点的去磷酸化。芦丁还具有特异性作用，因为它对PA有血管舒张作用，而对MA没有。
