Huai Ruituo, Han Xiaohua, Wang Bingxiang, Li Chunlin, Niu Yawen, Li Ran, Qu Zhiqiang
Department of Physiology, Qingdao University Medical College, Qingdao, China.
Am J Hypertens. 2014 May;27(5):750-60. doi: 10.1093/ajh/hpt220. Epub 2013 Dec 6.
Although 7,8-dihydroxyflavone (7,8-DHF) has been demonstrated to be potently neuroprotective, its effect on vascular function remains unknown.
The effect of 7,8-DHF on phenylephrine (PE)-induced preconstriction was examined with aortic rings isolated from normal rats. Its effective mechanisms were studied with blockers, Western blotting, and primarily cultured vascular smooth myocytes. The blood pressure (BP) of rats was measured with a tail cuff method.
7,8-DHF dose-dependently dilated the PE-preconstricted, endothelia-intact aortic rings with concentration for 50% of maximal effect (EC50) of approximately 24 µM. Both Nω-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylyl cyclase blocker, significantly reduced the vasorelaxing effect of 7,8-DHF. Western blotting showed that 7,8-DHF increased the aortic endothelial nitric oxide synthase protein expression and phosphorylation. With endothelia removed, 7,8-DHF also dilated the PE-preconstricted rings but with EC50 of approximately 104 µM. Ca(2+) imaging experiments detected that 7,8-DHF probably blocked both intracellular Ca(2+) release and extracellular Ca(2+) influx. Therefore, the mechanisms of 7,8-DHF dilating effect might be stimulating the nitric oxide/cGMP production and blocking the Ca(2+) signaling pathway instead of tropomyosin receptor kinase B receptors because ANA-12, its specific antagonist, did not show any effect against 7,8-DHF. When administered intravenously, 7,8-DHF significantly reduced the BP of the spontaneously hypertensive rats. However, when used orally, there was only a slight but significant reduction in the diastolic pressure.
The results suggest that neuro-protective 7,8-DHF is also a vasorelaxing and antihypertensive substance in rats.
尽管已证明7,8 - 二羟基黄酮（7,8 - DHF）具有强大的神经保护作用，但其对血管功能的影响仍不清楚。
用从正常大鼠分离的主动脉环检测7,8 - DHF对去氧肾上腺素（PE）诱导的预收缩的影响。用阻滞剂、蛋白质免疫印迹法和原代培养的血管平滑肌细胞研究其作用机制。用尾套法测量大鼠血压（BP）。
7,8 - DHF以剂量依赖方式使PE预收缩的、内皮完整的主动脉环舒张，最大效应浓度的50%（EC50）约为24 μM。一氧化氮合酶抑制剂盐酸Nω - 硝基 - L - 精氨酸甲酯和可溶性鸟苷酸环化酶阻滞剂1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮均显著降低7,8 - DHF的血管舒张作用。蛋白质免疫印迹显示7,8 - DHF增加主动脉内皮型一氧化氮合酶蛋白表达和磷酸化。去除内皮后，7,8 - DHF也使PE预收缩的环舒张，但EC50约为104 μM。Ca(2+)成像实验检测到7,8 - DHF可能同时阻断细胞内Ca(2+)释放和细胞外Ca(2+)内流。因此，7,8 - DHF舒张作用的机制可能是刺激一氧化氮/cGMP生成并阻断Ca(2+)信号通路，而非原肌球蛋白受体激酶B受体，因为其特异性拮抗剂ANA - 12对7,8 - DHF无任何作用。静脉注射时，7,8 - DHF显著降低自发性高血压大鼠的血压。然而，口服时，仅舒张压有轻微但显著的降低。
结果表明，具有神经保护作用的7,8 - DHF在大鼠中也是一种血管舒张和降压物质。
