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The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway.
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2020-07-01 , DOI: 10.1124/pr.120.019240 V Kapil 1 , R S Khambata 1 , D A Jones 1 , K Rathod 1 , C Primus 1 , G Massimo 1 , J M Fukuto 1 , A Ahluwalia 2
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2020-07-01 , DOI: 10.1124/pr.120.019240 V Kapil 1 , R S Khambata 1 , D A Jones 1 , K Rathod 1 , C Primus 1 , G Massimo 1 , J M Fukuto 1 , A Ahluwalia 2
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In contrast to nitric oxide, which has well established and important roles in the regulation of blood flow and thrombosis, neurotransmission, the normal functioning of the genitourinary system, and the inflammation response and host defense, its oxidized metabolites nitrite and nitrate have, until recently, been considered to be relatively inactive. However, this view has been radically revised over the past decade and more. Much evidence has now accumulated demonstrating that nitrite serves as a storage form of nitric oxide, releasing nitric oxide preferentially under acidic and/or hypoxic conditions but also occurring under physiologic conditions: a phenomenon that is catalyzed by a number of distinct mammalian nitrite reductases. Importantly, preclinical studies demonstrate that reduction of nitrite to nitric oxide results in a number of beneficial effects, including vasodilatation of blood vessels and lowering of blood pressure, as well as cytoprotective effects that limit the extent of damage caused by an ischemia/reperfusion insult, with this latter issue having been translated more recently to the clinical setting. In addition, research has demonstrated that the other main metabolite of the oxidation of nitric oxide (i.e., nitrate) can also be sequentially reduced through processing in vivo to nitrite and then nitrite to nitric oxide to exert a range of beneficial effects—most notably lowering of blood pressure, a phenomenon that has also been confirmed recently to be an effective method for blood pressure lowering in patients with hypertension. This review will provide a detailed description of the pathways involved in the bioactivation of both nitrate and nitrite in vivo, their functional effects in preclinical models, and their mechanisms of action, as well as a discussion of translational exploration of this pathway in diverse disease states characterized by deficiencies in bioavailable nitric oxide.
中文翻译：
体内产生一氧化氮的非规范途径：硝酸盐-亚硝酸盐-一氧化氮途径。
一氧化氮在调节血流和血栓形成，神经传递，泌尿泌尿系统的正常功能以及炎症反应和宿主防御中具有公认的重要作用，其氧化代谢产物亚硝酸盐和硝酸盐直到最近，被认为是相对不活跃的。但是，在过去的十多年中，这种观点已经得到了彻底的修改。现在已经积累了许多证据，证明亚硝酸盐作为一氧化氮的储存形式，在酸性和/或低氧条件下优先释放一氧化氮，但在生理条件下也可能发生：这种现象是由多种不同的哺乳动物亚硝酸盐还原酶催化的。重要的，临床前研究表明，将亚硝酸盐还原为一氧化氮会产生许多有益的作用，包括血管舒张和血压降低，以及细胞保护作用，这些作用限制了缺血/再灌注损伤所引起的损害程度。最近一期已被翻译成临床。此外，研究表明一氧化氮的另一种主要代谢产物（即硝酸盐）也可以通过在体内加工成亚硝酸盐然后再由亚硝酸盐转化为一氧化氮而被依次还原，从而产生一系列有益的作用-最显着的是降低血压升高这一现象最近也被证实是降低高血压患者血压的有效方法。
更新日期：2020-06-24
中文翻译：
体内产生一氧化氮的非规范途径：硝酸盐-亚硝酸盐-一氧化氮途径。
一氧化氮在调节血流和血栓形成，神经传递，泌尿泌尿系统的正常功能以及炎症反应和宿主防御中具有公认的重要作用，其氧化代谢产物亚硝酸盐和硝酸盐直到最近，被认为是相对不活跃的。但是，在过去的十多年中，这种观点已经得到了彻底的修改。现在已经积累了许多证据，证明亚硝酸盐作为一氧化氮的储存形式，在酸性和/或低氧条件下优先释放一氧化氮，但在生理条件下也可能发生：这种现象是由多种不同的哺乳动物亚硝酸盐还原酶催化的。重要的，临床前研究表明，将亚硝酸盐还原为一氧化氮会产生许多有益的作用，包括血管舒张和血压降低，以及细胞保护作用，这些作用限制了缺血/再灌注损伤所引起的损害程度。最近一期已被翻译成临床。此外，研究表明一氧化氮的另一种主要代谢产物（即硝酸盐）也可以通过在体内加工成亚硝酸盐然后再由亚硝酸盐转化为一氧化氮而被依次还原，从而产生一系列有益的作用-最显着的是降低血压升高这一现象最近也被证实是降低高血压患者血压的有效方法。
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