NAD(P)H oxidase-derived hydrogen peroxide mediates endothelial nitric oxide production in response to angiotensin
NAD(P)H oxidase-derived hydrogen peroxide mediates endothelial nitric oxide production in response to angiotensin
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DOI：
10.1074/jbc.m208884200
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发表时间：
2002-12-13
影响因子：
4.8
通讯作者：
Harrison, DG
中科院分区：
文献类型：
--
作者：
Cai, H;Li, ZM;Harrison, DG
最近有研究表明，外源性过氧化氢(H_2O_2)的加入增加了内皮一氧化氮(NO.)制作。目前的研究旨在确定内源性过氧化氢水平是否足以刺激NO。在完整的内皮细胞中产生。不是的。产物通过NO特异的微电极或使用Fe2+-(DETC)(2)作为NO特异的自旋陷阱的电子自旋共振谱来检测。在牛主动脉内皮细胞中加入H_2O_2后，NO含量显著增加，且呈剂量依赖性。放手。与血管紧张素II(10(-7)摩尔)孵育后，细胞内过氧化氢水平升高，但可被聚乙二醇过氧化氢酶减弱。血管紧张素II使NO的生成增加2倍，这可被氯沙坦和聚乙二醇过氧化氢酶阻止，这表明AT1受体和H_2O_2在这一反应中起着关键作用。相比之下，没有。由缓激肽或钙离子载体A23187诱导的产物不受聚乙二醇-过氧化氢酶的影响。与牛主动脉内皮细胞一样，血管紧张素II使NO倍增。C57BL/6小鼠主动脉内皮细胞产生NO，但对NO无影响。P47(Phox-/-)小鼠内皮细胞的产生。相反，A23187刺激NO。野生型和p47(Phox-/-)小鼠的内皮细胞产生类似的程度。综上所述，本研究提供了来自NAD(P)H氧化酶的内源性过氧化氢介导内皮细胞一氧化氮的直接证据。血管紧张素II的反应产生。在与血管紧张素II水平升高相关的疾病条件下，这种反应可能代表一种代偿机制。由于血管紧张素II还刺激NAD(P)H氧化酶产生O-2((中心圆点))，因此H_2O_2对NO的刺激作用。可能促进过氧亚硝酸盐的形成，以响应该八肽。
Recently, it has been shown that the exogenous addition of hydrogen peroxide (H2O2) increases endothelial nitric oxide (NO.) production. The current study is designed to determine whether endogenous levels of H2O2 are ever sufficient to stimulate NO. production in intact endothelial cells. NO. production was detected by a NO.- specific microelectrode or by an electron spin resonance spectroscopy using Fe2+-(DETC)(2) as a NO.-specific spin trap. The addition of H2O2 to bovine aortic endothelial cells caused a potent and dose-dependent increase in NO. release. Incubation with angiotensin II (10(-7) mol) elevated intracellular H2O2 levels, which were attenuated with PEG-catalase. Angiotensin II increased NO' production by 2-fold, and this was prevented by Losartan and by PEG-catalase, suggesting a critical role of AT1 receptor and H2O2 in this response. In contrast, NO. production evoked by either bradykinin or calcium ionophore A23187 was unaffected by PEG-catalase. As in bovine aortic endothelial cells, angiotensin II doubled NO. production in aortic endothelial cells from C57BL/6 mice but had no effect on NO. production in endothelial cells from p47(phox-/-) mice. In contrast, A23187 stimulated NO. production to a similar extent in endothelial cells from wild-type and p47(phox-/-) mice. In summary, the present study provides direct evidence that endogenous H2O2, derived from the NAD(P)H oxidase, mediates endothelial NO. production in response to angiotensin II. Under disease conditions associated with elevated levels of angiotensin II, this response may represent a compensatory mechanism. Because angiotensin II also stimulates O-2((center dot) over bar) production from the NAD(P)H oxidase, the H2O2 stimulation of NO. may facilitate peroxynitrite formation in response to this octapeptide.