Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide.
Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide.
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DOI：
10.1093/cvr/cvp235
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发表时间：
2009-11-01
影响因子：
10.8
通讯作者：
Griffith TM
中科院分区：
文献类型：
--
作者：
Garry A;Edwards DH;Fallis IF;Jenkins RL;Griffith TM
我们的目的是调查是否抗坏血酸（AA）和四氢生物蝶呤（BH 4）的促氧化性能调节内皮依赖性，电紧张介导的动脉舒张。在对兔髂动脉（RIA）环的研究中，AA（1 mM）和BH 4（200 µM）可增强由肌质内质网Ca 2 +-ATP酶抑制剂环匹阿尼酸和G蛋白偶联激动剂乙酰胆碱（ACh）诱发的NO非依赖性内皮源性超极化因子（EDHF）型舒张，其产生的缓冲液浓度范围为40-80 µM的H2 O2。外源性H2 O2增强环匹阿尼酸（CPA）和乙酰胆碱（ACh）诱发的舒张作用，阈值为10-30 µM，AA和BH 4的增强作用被过氧化氢酶消除，过氧化氢酶破坏了器官室中这些试剂氧化产生的H2 O2。外膜应用H2 O2也增强了EDHF型扩张反应引起的CPA和ACh RIA段灌注管腔内与H2 O2-自由缓冲液，虽然与降低的功效。在RIA环中，通过连接蛋白模拟肽（YDKSFPISHVR和SRPTEK）靶向RIA中表达的占主导地位的血管连接蛋白的第一和第二细胞外环阻断间隙连接，克服了控制松弛和H2 O2增强。超氧化物歧化酶减弱的增强EDHF型弛豫BH 4，但不AA，与研究结果表明，超氧阴离子的H2 O2的产生由两个代理商的差异作用一致。AA和BH 4的促氧化作用可以通过产生H2 O2来增强EDHF现象，H2 O2先前已被证明通过促进Ca 2+从内皮商店释放来放大电紧张性超极化介导的松弛。
Our objective was to investigate whether pro-oxidant properties of ascorbic acid (AA) and tetrahydrobiopterin (BH4) modulate endothelium-dependent, electrotonically mediated arterial relaxation. In studies with rabbit iliac artery (RIA) rings, NO-independent, endothelium-derived hyperpolarizing factor (EDHF)-type relaxations evoked by the sarcoplasmic endoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid and the G protein-coupled agonist acetylcholine (ACh) were enhanced by AA (1 mM) and BH4 (200 µM), which generated buffer concentrations of H2O2 in the range of 40–80 µM. Exogenous H2O2 potentiated cyclopiazonic acid (CPA)- and ACh-evoked relaxations with a threshold of 10–30 µM, and potentiation by AA and BH4 was abolished by catalase, which destroyed H2O2 generated by oxidation of these agents in the organ chamber. Adventitial application of H2O2 also enhanced EDHF-type dilator responses evoked by CPA and ACh in RIA segments perfused intraluminally with H2O2-free buffer, albeit with reduced efficacy. In RIA rings, both control relaxations and their potentiation by H2O2 were overcome by blockade of gap junctions by connexin-mimetic peptides (YDKSFPISHVR and SRPTEK) targeted to the first and second extracellular loops of the dominant vascular connexins expressed in the RIA. Superoxide dismutase attenuated the potentiation of EDHF-type relaxations by BH4, but not AA, consistent with findings demonstrating a differential role for superoxide anions in the generation of H2O2 by the two agents. Pro-oxidant effects of AA and BH4 can enhance the EDHF phenomenon by generating H2O2, which has previously been shown to amplify electrotonic hyperpolarization-mediated relaxation by facilitating Ca2+ release from endothelial stores.
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DOI：
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发表时间：
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影响因子：
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