Bryan Nathan S
Institute of Molecular Medicine, University of Texas at Houston Health Sciences Center, 1825 Pressler, Houston, TX 77030, USA.
Free Radic Biol Med. 2006 Sep 1;41(5):691-701. doi: 10.1016/j.freeradbiomed.2006.05.019. Epub 2006 May 23.
All life requires nitrogen compounds. Nitrite is such a compound that is naturally occurring in nature and biology. Over the years, the pharmacological stance on nitrite has undergone a surprising metamorphosis, from a vilified substance that generates carcinogenic nitrosamines in the stomach to a life-saving drug that liberates a protective agent (nitric oxide or NO) during hypoxic events. Nitrite has been investigated as a vasodilator in mammals for over 125 years and is a known by-product of organic nitrate metabolism. There has been a recent rediscovery of some of the vasodilator actions of nitrite in physiology along with novel discoveries which render nitrite a fundamental molecule in biology. Until recently nitrite was thought to be an inert oxidative breakdown product of endogenous NO synthesis but the past few years have focused on the reduction of nitrite back to NO in the circulation as a possible mechanism for hypoxic vasodilatation. Nitrite has evolved into an endogenous signaling molecule and regulator of gene expression that may not only serve as a diagnostic marker but also find its role as a potential therapeutic agent of cardiovascular disease. These data therefore warrant a reevaluation on the fate and metabolism of nitrite in biological systems. This review serves to encompass the history and recent evolution of nitrite, the compartment-specific metabolism of nitrite and its role in plasma as a biomarker for disease, the role of nitrite as a potential regulator of NO homeostasis, and the future of nitrite-based research.
所有生命都需要含氮化合物。亚硝酸盐就是这样一种在自然界和生物体内天然存在的化合物。多年来，关于亚硝酸盐的药理学观点经历了惊人的转变，从一种在胃中会产生致癌亚硝胺的有害物质，变成了一种在缺氧情况下能释放保护剂（一氧化氮或NO）的救命药物。在哺乳动物中，亚硝酸盐作为血管扩张剂已被研究了超过125年，并且是有机硝酸盐代谢的已知副产品。最近，人们重新发现了亚硝酸盐在生理学中的一些血管扩张作用，同时还有一些新发现使亚硝酸盐成为生物学中的一种基本分子。直到最近，亚硝酸盐还被认为是内源性一氧化氮合成的一种惰性氧化分解产物，但在过去几年里，人们关注的焦点是循环中亚硝酸盐还原为一氧化氮，这可能是缺氧性血管舒张的一种机制。亚硝酸盐已演变成一种内源性信号分子和基因表达调节剂，它不仅可以作为诊断标志物，还可能在心血管疾病的治疗中发挥作用。因此，这些数据有必要对生物系统中亚硝酸盐的命运和代谢进行重新评估。这篇综述旨在涵盖亚硝酸盐的历史和近期演变、亚硝酸盐在特定区域的代谢及其在血浆中作为疾病生物标志物的作用、亚硝酸盐作为一氧化氮稳态潜在调节剂的作用，以及基于亚硝酸盐的研究的未来。
