The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

中文翻译：

---

一氧化氮和过氧亚硝酸盐在健康和疾病中的作用。

哺乳动物细胞具有合成自由基一氧化氮（NO）能力的发现，为生物学和医学各个领域的科学研究带来了非凡的推动力。自从早期被描述为内皮源性松弛因子以来，NO 已成为调节几乎所有关键细胞功能的基本信号装置，以及多种条件下细胞损伤的有效介质。最近的证据表明，大部分由 NO 引起的细胞毒性是由过氧亚硝酸盐引起的，过氧亚硝酸盐是由 NO 与另一种自由基（超氧阴离子）之间的扩散控制反应产生的。过氧亚硝酸盐通过直接氧化反应或通过间接的自由基介导机制与脂质、DNA 和蛋白质相互作用。这些反应触发细胞反应，从细胞信号传导的微妙调节到压倒性的氧化损伤，使细胞坏死或凋亡。在体内，过氧亚硝酸盐的生成是中风、心肌梗塞、慢性心力衰竭、糖尿病、循环性休克、慢性炎症性疾病、癌症和神经退行性疾病等疾病的重要致病机制。因此，旨在去除过氧亚硝酸盐的新药理学策略可能代表未来强大的治疗工具。本综述详细介绍了支持一氧化氮和过氧亚硝酸盐这些新作用的证据。