Nitrite as a Source of Bioactive Nitric Oxide

摘要：一氧化氮（NO）是一种由内皮细胞连续合成的可溶气体，通过激活血管平滑肌中的冠状动脉和全身循环中的冠状动脉酰环化酶，对血管舒张张力起重要作用。然而，冠状动脉疾病患者由于内皮损伤或功能障碍，一氧化氮合成不足或降解增加。一氧化氮的降低可通过血管收缩、血小板活化、炎症细胞附着于动脉壁以及血管壁细胞成分生长增加等途径促进冠状动脉疾病的症状和进展。我们最近确定，由NO自动氧化形成的亚硝酸盐可以转化为生物活性NO，部分通过与脱氧血红素蛋白的反应，脱氧血红素蛋白不仅存在于红细胞中，而且存在于血管壁内。生物活性一氧化氮的另一种来源可能是通过饮食，因为蔬菜和腌肉中的硝酸盐可以通过口腔细菌中硝酸盐还原酶的作用转化为亚硝酸盐。亚硝酸盐可在胃内的酸性环境中转化为NO并被吸收到血液中，或直接被吸收并与脱氧血红素蛋白反应在血液中转化为NO。本研究旨在确定饮食中硝酸盐/亚硝酸盐对血液中一氧化氮加合物和血管扩张张力的贡献，通过前臂直接评估和通过跑步机运动测试间接评估。本研究的发现可能不仅对冠状动脉疾病，而且对其他与局部内皮功能障碍和内皮NO生物活性降低相关的疾病（如高血压、糖尿病、高胆固醇血症、吸烟、雌激素缺乏）具有重要的临床意义，并可能解释流行病学调查研究中显示的富含蔬菜的饮食对心血管的益处。

Summary: Precis: Nitric oxide (NO) is a soluble gas continuously synthesized by the endothelium that contributes importantly to vasodilator tone of the coronary and systemic circulations by activating guanylyl cyclase in vascular smooth muscle. Patients with coronary artery disease, however, have deficient synthesis or increased degradation of NO due to endothelial damage or dysfunction. Reduced NO could contribute to symptoms and progression of coronary artery disease through vasoconstriction, platelet activation, inflammatory cell attachment to the arterial wall, and increased growth of cellular elements of the vessel wall. We have recently determined that nitrite, formed by the auto-oxidation of NO, can be converted to bioactive NO, in part through reactions with deoxyheme proteins that exist not only in red blood cells, but also within the vessel wall. An alternative source of bioactive NO may be via the diet, as nitrates found in vegetables and cured meats may be converted to nitrite by action of nitrate reductases present in oral bacteria. Nitrite may then be converted to NO within the acidic environment in the stomach and absorbed into the bloodstream, or absorbed directly and converted to NO in the bloodstream via reaction with deoxyheme proteins. This study is designed to determine the contribution of dietary nitrate/nitrite to NO adducts in blood and to vascular dilator tone assessed directly in the forearm and indirectly through treadmill exercise testing. Findings in this study may have important clinical implications not only in coronary artery disease, but also in other conditions associated with regional endothelial dysfunction and reduced endothelial NO bioactivity (e.g., hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, estrogen deficiency), and possibly account for the cardiovascular benefit of diets rich in vegetables shown in epidemiological survey studies.