Nitrite as a Source of Bioactive Nitric Oxide

总结：精确度：一氧化氮（NO）是一种由内皮细胞持续合成的可溶性气体，其通过激活血管平滑肌中的鸟苷酸环化酶而对冠状动脉和体循环的血管舒张张力做出重要贡献。然而，患有冠状动脉疾病的患者由于内皮损伤或功能障碍而具有NO的合成不足或降解增加。NO减少可通过血管收缩、血小板活化、炎性细胞附着于动脉壁和血管壁细胞成分生长增加而导致冠状动脉疾病的症状和进展。我们最近已经确定，由NO的自氧化形成的亚硝酸盐可以部分地通过与不仅存在于红细胞中而且存在于血管壁内的脱氧血红素蛋白反应而转化为生物活性NO。生物活性NO的另一种来源可能是通过饮食，因为蔬菜和腌肉中发现的硝酸盐可以通过口腔细菌中存在的硝酸盐还原酶的作用转化为亚硝酸盐。亚硝酸盐然后可以在胃中的酸性环境中转化为NO并吸收到血流中，或者直接吸收并通过与脱氧血红素蛋白反应在血流中转化为NO。本研究旨在确定饮食中硝酸盐/亚硝酸盐对血液中NO加合物的贡献，以及直接在前臂和间接通过跑步机运动试验评估的血管扩张张力。这项研究的发现不仅在冠状动脉疾病中，而且在与局部内皮功能障碍和内皮NO生物活性降低相关的其他疾病中（例如，高血压、糖尿病、高胆固醇血症、吸烟、雌激素缺乏症），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.