Beckman J S, Koppenol W H
Department of Anesthesiology, University of Alabama at Birmingham 35233, USA.
Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37. doi: 10.1152/ajpcell.1996.271.5.C1424.
Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
一氧化氮与大多数细胞间信使不同，因为它能迅速且各向同性地扩散通过大多数组织，反应很少，但由于会被氧合血红蛋白迅速破坏，所以不能通过脉管系统运输。一氧化氮在细胞间的快速扩散使其能够局部整合血管对湍流的反应、调节神经元中的突触可塑性以及控制神经网络的振荡行为。一氧化氮不一定寿命短暂，其本身的反应性并不比氧气更强。在体外，一氧化氮本身的反应性被大大高估了，因为没有提供去除一氧化氮的途径。在微摩尔浓度下，一氧化氮能在溶液中持续存在几分钟，然后才与氧气反应形成更强的氧化剂如二氧化氮。在体内，一氧化氮通过扩散100微米穿过组织进入红细胞并与氧合血红蛋白反应，在几秒钟内被清除。一氧化氮的直接毒性较小，但与超氧化物反应形成过氧亚硝酸根（ONOO-）时，毒性会大大增强。一氧化氮是唯一能以足够高的浓度产生从而在超氧化物歧化酶竞争超氧化物时胜出的生物分子。过氧亚硝酸根与大多数生物分子的反应相对较慢，这使得过氧亚硝酸根成为一种选择性氧化剂。过氧亚硝酸根会修饰蛋白质中的酪氨酸以产生硝基酪氨酸，在体内留下可检测的痕迹。对包括神经丝和肌动蛋白在内的结构蛋白的硝化作用会破坏细丝组装，产生重大的病理后果。抗硝基酪氨酸抗体已揭示在人类动脉粥样硬化、心肌缺血、脓毒症和窘迫肺、炎症性肠病以及肌萎缩侧索硬化中存在硝化作用。
