Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment
Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment
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DOI：
10.1152/ajpheart.00448.2003
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发表时间：
2003-12-01
影响因子：
4.8
通讯作者：
Koller, A
中科院分区：
文献类型：
--
作者：
Bagi, Z;Cseko, C;Koller, A
我们的目的是测试这一假设，即活性氧（ROS）的水平增加是主要负责的一氧化氮（NO）介导的调节高同型半胱氨酸（HHcy）的小动脉壁切应力（WSS）的损害。因此，研究了从对照（血清Hcy：6+/-1 μ M）、甲硫氨酸饮食诱导的HHcy大鼠（4周，血清Hcy：30+/-6 μ M）和用维生素C（一种已知的抗氧化剂）处理的HHcy大鼠（4周，150mg.kg.天;血清Hcy：32+/-10 μ M）分离的加压股薄肌小动脉（基底直径：类似于170 μ m）的流动/WSS诱导的扩张。在HHcy大鼠的血管中，管腔内流量/WSS诱导的扩张的增加被转换为收缩。N-ω-硝基-L-精氨酸甲酯（L-NAME）抑制NO合成不影响收缩。维生素C治疗HHcy大鼠逆转WSS诱导的小动脉收缩L-NAME敏感性扩张，但不影响控制反应。对于钙离子载体A-23187，获得了类似的响应变化。此外，舒张压和平均动脉血压和血清8-异前列腺素水平（体内氧化应激的标志物）显着升高，在大鼠与HHcy，维生素C治疗正常化的变化。两者合计，我们的数据表明，在慢性高同型半胱氨酸长期维生素C治疗，通过降低体内氧化应激，增强NO的生物利用度，恢复小动脉中的剪切应力的调节，和正常化的全身血压。因此，我们的研究提供的证据表明，氧化应激是一个重要的体内机制，是主要负责的发展内皮失调的WSS在HHcy。
We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: similar to170 mum) isolated from control (serum Hcy: 6+/-1 muM), methionine diet-induced HHcy rats (4 wk, serum Hcy: 30+/-6 muM), and HHcy rats treated with vitamin C, a known antioxidant (4 wk, 150 mg.kg body wt(-1).day(-1); serum Hcy: 32+/-10 muM), were investigated. In vessels of HHcy rats, increases in intraluminal flow/WSS-induced dilations were converted to constrictions. Constrictions were unaffected by inhibition of NO synthesis by N-omega-nitro-L-arginine methyl ester (L-NAME). Vitamin C treatment of HHcy rats reversed the WSS-induced arteriolar constrictions to L-NAME-sensitive dilations but did not affect control responses. Similar changes in responses were obtained for the calcium ionophore A-23187. In addition, diastolic and mean arterial blood pressure and serum 8-isoprostane levels (a marker of in vivo oxidative stress) were significantly elevated in rats with HHcy, changes that were normalized by vitamin C treatment. Taken together, our data show that in chronic HHcy long-term vitamin C treatment, by decreasing oxidative stress in vivo, enhanced NO bioavailability, restored the regulation of shear stress in arterioles, and normalized systemic blood pressure. Thus our study provides evidence that oxidative stress is an important in vivo mechanism that is primarily responsible for the development of endothelial dysregulation of WSS in HHcy.