Dezfulian Cameron, Raat Nicolaas, Shiva Sruti, Gladwin Mark T
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cardiovasc Res. 2007 Jul 15;75(2):327-38. doi: 10.1016/j.cardiores.2007.05.001. Epub 2007 May 10.
The anion nitrite (NO(2)(-)) constitutes a biochemical reservoir for nitric oxide (NO). Nitrite reduction to NO may be catalyzed by hemoglobin, myoglobin or other metal-containing enzymes and occurs at increasing rates under conditions of physiologic hypoxia or ischemia. A number of laboratories have now demonstrated in animal models the ability of nitrite to provide potent cytoprotection following focal ischemia-reperfusion (IR) injury of the heart, liver, brain, and kidney. While the mechanism of nitrite-mediated cytoprotection remains to be fully characterized, the release of nitrite-derived NO following IR appears to be central to this mechanism. The evidence of nitrite-mediated cytoprotection against IR injury in multiple animal models opens the door to potential therapeutic opportunities in human disease. Here we review the mechanisms for nitrite formation in blood and tissue, its metabolic equilibrium with NO, nitrate, and NO-modified proteins, the evidence supporting nitrite-mediated cytoprotection, and the potential mechanisms driving cytoprotection, and we explore the opportunities for the therapeutic application of nitrite for human disease.
亚硝酸根阴离子（NO₂⁻）是一氧化氮（NO）的生化储存库。亚硝酸还原为NO可由血红蛋白、肌红蛋白或其他含金属酶催化，并且在生理性缺氧或缺血条件下反应速率会增加。现在许多实验室已在动物模型中证明，亚硝酸在心脏、肝脏、脑和肾脏局灶性缺血再灌注（IR）损伤后具有强大的细胞保护能力。虽然亚硝酸介导的细胞保护机制仍有待充分阐明，但IR后源自亚硝酸的NO释放似乎是该机制的核心。在多个动物模型中，亚硝酸介导的针对IR损伤的细胞保护证据为人类疾病的潜在治疗机会打开了大门。在此，我们综述了血液和组织中亚硝酸形成的机制、其与NO、硝酸盐及NO修饰蛋白的代谢平衡、支持亚硝酸介导细胞保护的证据、驱动细胞保护的潜在机制，并探讨了亚硝酸在人类疾病治疗应用中的机会。
