Liu Yien, Buerk Donald G, Barbee Kenneth A, Jaron Dov
School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
Nitric Oxide. 2016 Nov 30;60:1-9. doi: 10.1016/j.niox.2016.08.003. Epub 2016 Aug 24.
Nitrite infusion into the bloodstream has been shown to elicit vasodilation and protect against ischemia-reperfusion injury through nitric oxide (NO) release in hypoxic conditions. However, the mechanism by which nitrite-derived NO escapes scavenging by hemoglobin in the erythrocyte has not been fully elucidated, owing in part to the difficulty in measuring the reactions and transport on NO in vivo. We developed a mathematical model for an arteriole and surrounding tissue to examine the hypothesis that dinitrogen trioxide (NO) acts as a stable intermediate for preserving NO. Our simulations predict that with hypoxia and moderate nitrite concentrations, the NO pathway can significantly preserve the NO produced by hemoglobin nitrite reductase in the erythrocyte and elevate NO reaching the smooth muscle cells. Nitrite retains its ability to increase NO bioavailability even at varying flow conditions, but there is minimal effect under normoxia or very low nitrite concentrations. Our model demonstrates a viable pathway for reconciling experimental findings of potentially beneficial effects of nitrite infusions despite previous models showing negligible NO elevation associated with hemoglobin nitrite reductase. Our results suggest that additional mechanisms may be needed to explain the efficacy of nitrite-induced vasodilation at low infusion concentrations.
已表明向血流中输注亚硝酸盐可引起血管舒张，并通过在缺氧条件下释放一氧化氮（NO）来预防缺血再灌注损伤。然而，亚硝酸盐衍生的NO在红细胞中逃避血红蛋白清除的机制尚未完全阐明，部分原因是难以在体内测量NO的反应和转运。我们开发了一种用于小动脉和周围组织的数学模型，以检验三氧化二氮（N₂O₃）作为保存NO的稳定中间体这一假设。我们的模拟预测，在缺氧和适度亚硝酸盐浓度下，NO途径可显著保存红细胞中亚硝酸血红蛋白还原酶产生的NO，并提高到达平滑肌细胞的NO水平。即使在不同的血流条件下，亚硝酸盐仍保持其增加NO生物利用度的能力，但在常氧或极低亚硝酸盐浓度下影响极小。我们的模型展示了一条可行的途径，可调和亚硝酸盐输注潜在有益作用的实验结果，尽管先前的模型显示与亚硝酸血红蛋白还原酶相关的NO升高可忽略不计。我们的结果表明，可能需要其他机制来解释低输注浓度下亚硝酸盐诱导血管舒张的功效。
