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.
Microvasc Res. 2017 Jul;112:79-86. doi: 10.1016/j.mvr.2017.03.009. Epub 2017 Mar 28.
Interactions between cardiac myoglobin (Mb), nitrite, and nitric oxide (NO) are vital in regulating O storage, transport, and NO homeostasis. Production of NO through the reduction of endogenous myocardial nitrite by deoxygenated myoglobin has been shown to significantly reduce myocardial infarction damage and ischemic injury. We developed a mathematical model for a cardiac arteriole and surrounding myocardium to examine the hypothesis that myoglobin switches functions from being a strong NO scavenger to an NO producer via the deoxymyoglobin nitrite reductase pathway. Our results predict that under ischemic conditions of flow, blood oxygen level, and tissue pH, deoxyMb nitrite reduction significantly elevates tissue and smooth muscle cell NO. The size of the effect is consistent at different flow rates, increases with decreasing blood oxygen and tissue pH and, in extreme pathophysiological conditions, NO can even be elevated above the normoxic levels. Our simulations suggest that cardiac deoxyMb nitrite reduction is a plausible mechanism for preserving or enhancing NO levels using endogenous nitrite despite the rate-limiting O levels for endothelial NO production. This NO could then be responsible for mitigating deleterious effects under ischemic conditions.
心肌肌红蛋白（Mb）、亚硝酸盐和一氧化氮（NO）之间的相互作用在调节氧储存、运输和NO稳态方面至关重要。已表明通过脱氧肌红蛋白还原内源性心肌亚硝酸盐产生NO可显著减少心肌梗死损伤和缺血性损伤。我们建立了一个心肌小动脉和周围心肌的数学模型，以检验肌红蛋白通过脱氧肌红蛋白亚硝酸盐还原酶途径从强NO清除剂转变为NO产生者这一假说。我们的结果预测，在血流、血氧水平和组织pH值的缺血条件下，脱氧Mb亚硝酸盐还原会显著提高组织和平滑肌细胞中的NO水平。在不同流速下，这种效应的大小是一致的，随着血氧和组织pH值的降低而增加，并且在极端病理生理条件下，NO甚至可以升高到高于常氧水平。我们的模拟表明，尽管内皮NO产生存在限速氧水平，但心肌脱氧Mb亚硝酸盐还原是一种利用内源性亚硝酸盐维持或提高NO水平的合理机制。这种NO随后可能负责减轻缺血条件下的有害影响。
