Effect of dietary nitrate levels on nitrate fluxes in rat skeletal muscle and liver
Effect of dietary nitrate levels on nitrate fluxes in rat skeletal muscle and liver
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DOI：
10.1016/j.niox.2018.01.010
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发表时间：
2018-05-01
影响因子：
3.9
通讯作者：
Piknova, Barbora
中科院分区：
文献类型：
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作者：
Gilliard, Cameron N.;Lam, Jeff K.;Piknova, Barbora
啮齿动物骨骼肌具有高水平的硝酸根离子，并且这种内源性硝酸盐储库可以在运动期间为肌肉中的功能性充血和/或其他生理过程提供亚硝酸盐/一氧化氮（NO）。NOS1基因敲除的小鼠肌肉硝酸盐水平显著降低，表明NOS产生NO，并与氧合肌红蛋白反应作为硝酸盐的来源。然而，氧气水平通常在大多数内脏器官中较低，这提高了硝酸盐衍生的NO途径即使在"常氧"下也具有生理重要性的可能性，并且当外源性（膳食）硝酸盐摄入量低时，肌肉硝酸盐储库是主要的内源性NO备份。利用饮食硝酸盐操作，我们探讨了饮食对维持和更新肌肉硝酸盐库及其在其他组织中的水平的重要性。我们发现，当饮食中硝酸盐含量低时，骨骼肌硝酸盐被广泛使用。一周的硝酸盐饥饿导致骨骼肌中硝酸盐的急剧消耗和肝脏中的大量减少。在饥饿期间从骨骼肌中耗尽的硝酸盐从新的饮食来源中迅速恢复，与未遭受硝酸盐饥饿的动物相比，具有意想不到的显著"过载"。我们的研究结果表明，与内源性NOS来源相比，膳食硝酸盐对肌肉和其他组织中硝酸盐储备的重要性。这需要一个主动的运输机制，将硝酸盐隔离到细胞中，由缺乏饮食硝酸盐或其他酶的变化刺激。这些结果证实了肌肉是哺乳动物硝酸盐主要储存场所的假设。
Rodent skeletal muscle has high levels of nitrate ions and this endogenous nitrate reservoir can supply nitrite/nitric oxide (NO) for functional hyperemia and/or for other physiological processes in muscle during exercise. Mice with a NOS1 knockout have markedly reduced muscle nitrate levels, suggesting NO production by NOS and its reaction with oxymyoglobin as a source of nitrate. However, oxygen levels are normally low in most internal organs, which raises the possibility that nitrate-derived NO pathway is physiologically important even at "normoxia", and muscle nitrate reservoir is the main endogenous NO backup when exogeneous (dietary) nitrate intake is low. Using dietary nitrate manipulations, we explore the importance of diet for maintaining and renewal of muscle nitrate reservoir and its levels in other tissues. We found that skeletal muscle nitrate is extensively used when nitrate in diet is low. One week of nitrate starvation leads to dramatic nitrate depletion in skeletal muscle and a substantial decrease in liver. Nitrate depleted from skeletal muscle during starvation is quickly recovered from new dietary sources, with an unexpected significant "overload" compared with animals not subjected to nitrate starvation. Our results suggest the importance of dietary nitrate for nitrate reserves in muscle and in other tissues, when compared with endogenous NOS-derived sources. This requires an active transport mechanism for sequestering nitrate into cells, stimulated by lack of dietary nitrate or other enzymatic changes. These results confirm the hypothesis that muscle is a major storage site for nitrate in mammals.