Davis Heart and Lung Research Institute, The Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, 473 West 12th Avenue, Columbus, OH 43210, USA.
Nitric Oxide. 2010 Feb 15;22(2):83-90. doi: 10.1016/j.niox.2009.12.004. Epub 2010 Jan 5.
Nitric oxide (NO) is an important regulator of a variety of biological functions, and also has a role in the pathogenesis of cellular injury. It had been generally accepted that NO is solely generated in biological tissues by specific nitric oxide synthases (NOS) which metabolize arginine to citrulline with the formation of NO. However, over the last 15 years, nitrite-mediated NO production has been shown to be an important mechanism of NO formation in the heart and cardiovascular system. Now numerous studies have demonstrated that nitrite can be an important source rather than simply a product of NO in mammalian cells and tissues and can be a potential vasodilator drug for cardiovascular diseases. There are a variety of mechanisms of nitrite reduction to NO and it is now appreciated that this process, while enhanced under hypoxic conditions, also occurs under normoxia. Several methods, including electron paramagnetic resonance, chemiluminescence NO analyzer, and NO electrode have been utilized to measure, quantitate, and image nitrite-mediated NO formation. Results reveal that nitrite-dependent NO generation plays critical physiological and pathological roles, and is controlled by oxygen tension, pH, reducing substrates and nitrite levels. In this manuscript, we review the mechanisms of nitrite-mediated NO formation and the effects of oxygen on this process with a focus on how this occurs in the heart and vessels.
一氧化氮（NO）是多种生物功能的重要调节剂，在细胞损伤的发病机制中也具有作用。人们普遍认为，NO 仅由特定的一氧化氮合酶（NOS）在生物组织中产生，NOS 将精氨酸代谢为瓜氨酸，同时形成 NO。然而，在过去的 15 年中，亚硝酸盐介导的 NO 生成已被证明是心脏和心血管系统中 NO 形成的重要机制。现在，大量研究表明，亚硝酸盐可以是哺乳动物细胞和组织中 NO 的重要来源，而不仅仅是其简单的产物，并且可以作为心血管疾病的潜在血管扩张药物。亚硝酸盐还原为 NO 的机制多种多样，现在人们已经认识到，这个过程虽然在缺氧条件下增强，但在常氧条件下也会发生。已经利用多种方法，包括电子顺磁共振、化学发光 NO 分析仪和 NO 电极来测量、定量和成像亚硝酸盐介导的 NO 生成。结果表明，亚硝酸盐依赖性 NO 生成发挥着关键的生理和病理作用，并且受到氧张力、pH 值、还原底物和亚硝酸盐水平的控制。在本文中，我们综述了亚硝酸盐介导的 NO 生成的机制以及氧对此过程的影响，重点关注了其在心脏和血管中的发生机制。
