Nitric oxide - I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation
Nitric oxide - I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation
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DOI：
10.1152/ajpgi.1999.276.2.g315
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发表时间：
1999-02-01
影响因子：
4.5
通讯作者：
Wink, DA
中科院分区：
文献类型：
--
作者：
Grisham, MB;Jourd'Heuil, D;Wink, DA
一氧化氮（NO）在炎症中的作用是生理学中研究最多但争议最大的课题之一。大量研究表明NO具有抗炎作用，同时也有大量研究表明NO可促进炎症诱导的细胞和组织功能障碍。这些明显矛盾的观察结果的原因还不完全清楚，但是，我们建议，了解NO及其代谢产物的生理化学将提供一个蓝图，其中一个可以区分的监管/抗炎特性，NO从其有害/促炎作用。NO的生理化学是复杂的，包括许多潜在的反应。为了简化对这种化学的理解，NO化学的生理学方面可以分为直接和间接影响。这种类型的分类允许考虑NO的产生的时间、位置和速率以及可能受影响的相关目标。直接效应是其中NO直接与生物分子或靶标相互作用的那些反应，并且被认为在正常生理条件下当NO产生速率低时发生。一般来说，这些类型的反应可以起到调节和/或抗炎作用。另一方面，间接效应是由NO衍生的中间体介导的那些反应，例如由NO与氧或超氧化物反应衍生的反应性氮氧化物物质，并且当NO的通量增强时产生。我们假设这些类型的反应可能在活动性炎症期间占主导地位。考虑NO及其代谢产物的生理化学将有希望使人们能够确定许多NO依赖性反应中的哪些在调节炎症反应中是重要的，并且可能有助于设计用于治疗炎性组织损伤的新治疗策略。
The role of nitric oxide (NO) in inflammation represents one of the most studied yet controversial subjects in physiology. A number of reports have demonstrated that NO possesses potent anti-inflammatory properties, whereas an equally impressive number of studies suggest that NO may promote inflammation-induced cell and tissue dysfunction. The reasons for these apparent paradoxical observations are not entirely clear; however, we propose that understanding the physiological chemistry of NO and its metabolites will provide a blueprint by which one may distinguish the regulatory/anti-inflammatory properties of,NO from its deleterious/proinflammatory effects. The physiological chemistry of NO is complex and encompasses numerous potential reactions. In an attempt to simplify the understanding of this chemistry, the physiological aspects of NO chemistry may be categorized into direct and indirect effects. This type of classification allows for consideration of timing, location, and rate of production of NO and the relevant targets likely to be affected. Direct effects are those reactions in which NO interacts directly with a biological molecule or target and are thought to occur under normal physiological conditions when the rates of NO production are low. Generally, these types of reactions may serve regulatory and/or anti-inflammatory functions. Indirect effects, on the other hand, are those reactions mediated by NO-derived intermediates such as reactive nitrogen oxide species derived from the reaction of NO with oxygen or superoxide and are produced when fluxes of NO are enhanced. We postulate that these types of reactions may predominate during times of active inflammation. Consideration of the physiological chemistry of NO and its metabolites will hopefully allow one to identify which of the many NO-dependent reactions are important in modulating the inflammatory response and may help in the design of new therapeutic strategies for the treatment of inflammatory tissue injury.