PATHOLOGICAL IMPLICATIONS OF NITRIC-OXIDE, SUPEROXIDE AND PEROXYNITRITE FORMATION
PATHOLOGICAL IMPLICATIONS OF NITRIC-OXIDE, SUPEROXIDE AND PEROXYNITRITE FORMATION
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DOI：
10.1042/bst0210330
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发表时间：
1993-05-01
影响因子：
3.9
通讯作者：
CROW, JP
中科院分区：
文献类型：
--
作者：
BECKMAN, JS;CROW, JP
大约 6 年前，一氧化氮被确定为内皮源性舒张因子 (EDRF)，这是一种由硝酸甘油和硝普钠模仿的内源性血管舒张剂 [1-41。合成一氧化氮的组织种类繁多，在控制全身血压、呼吸、消化、阴茎勃起、血小板聚集、脑血流量和神经元突触可塑性方面发挥着重要作用[51。此外，一氧化氮或由其衍生的次级氧化剂有助于活化巨噬细胞和中性粒细胞的杀微生物和杀肿瘤活性[6, 7]。内皮和神经元通过钙调蛋白激活酶产生一氧化氮，该酶将精氨酸氧化为瓜氨酸，并需要生物蝶呤、NADPH 和氧气 [8, 91。生物蝶呤仍与酶紧密结合，并可在其中循环利用。一氧化氮合酶还含有 FAD、FMN 和铁血红素作为必需辅助因子。巨噬细胞酶不受钙调蛋白调节，基因序列揭示了大脑、内皮细胞和巨噬细胞酶之间的显着差异[101。病理状况可以显着上调一氧化氮的产生。受刺激的巨噬细胞和中性粒细胞通过诱导型不依赖于钙的一氧化氮合酶产生比内皮细胞显着更大的一氧化氮通量。内毒素（脂多糖）和细胞因子在许多通常不产生一氧化氮的组织中诱导不依赖于钙的一氧化氮合酶[ll]。例如，急性
Approximately 6 years ago, nitric oxide was identified as the endothelium-derived relaxing factor (EDRF), the endogenous vasodilator mimicked by nitroglycerin and nitroprusside [1-41. An astonishing variety of tissues synthesize nitric oxide, which has important roles in the control of systemic blood pressure, respiration, digestion, penile erection, platelet aggregation, cerebral blood flow and neuronal synaptic plasticity [51. Furthermore, nitric oxide, or a secondary oxidant derived from it, contributes to the microbicidal and tumoricidal activities of activated macrophages and neutrophils [6, 7]. Endothelium and neurons produce nitric oxide by a calmodulin-activated enzyme, which oxidizes arginine to citrulline and requires biopterin, NADPH and oxygen [8, 91. The biopterin remains tightly bound to the enzyme and may be recycled within it. Nitric oxide synthase also contains FAD, FMN and ferric haem as essential cofactors. The macrophage enzyme is not regulated by calmodulin, and gene sequences reveal significant differences between the brain, endothelial and macrophage enzymes [101. Pathological conditions can substantially upregulate the production of nitric oxide. Stimulated macrophages and neutrophils produce significantly greater fluxes of nitric oxide than endothelium by the inducible calcium-independent nitric oxide synthase. Endotoxin (lipopolysaccharide) and cytokines induce the calcium-independent nitric oxide synthase in many tissues that do not normally produce nitric oxide [ll]. For example, the acute