Grisham M B, Jourd'Heuil D, Wink D A
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
Am J Physiol. 1999 Feb;276(2):G315-21. doi: 10.1152/ajpgi.1999.276.2.G315.
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.
一氧化氮（NO）在炎症中的作用是生理学中研究最多但也最具争议的课题之一。许多报告表明，NO具有强大的抗炎特性，而同样数量可观的研究则表明，NO可能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尚不完全清楚；然而，我们认为，了解NO及其代谢产物的生理化学将提供一个蓝图，据此人们可以区分NO的调节/抗炎特性与其有害/促炎作用。NO的生理化学很复杂，包含许多潜在反应。为了简化对这种化学的理解，NO化学的生理方面可分为直接效应和间接效应。这种分类方式有助于考虑NO的产生时间、位置和速率以及可能受影响的相关靶点。直接效应是指NO直接与生物分子或靶点相互作用的反应，被认为在正常生理条件下，当NO产生速率较低时发生。一般来说，这类反应可能具有调节和/或抗炎功能。另一方面，间接效应是由NO衍生的中间体介导的反应，如NO与氧气或超氧化物反应产生的活性氮氧化物，当NO通量增加时产生。我们推测，这类反应可能在炎症活跃期占主导地位。考虑NO及其代谢产物的生理化学有望使人们确定众多依赖NO的反应中哪些在调节炎症反应中很重要，并可能有助于设计治疗炎症性组织损伤的新治疗策略。
