Three main nitrate reservoirs in the mammalian body

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Nitric oxide (NO) is a free radical with multiple functions in virtually all cells. In mammals, NO is generated by nitric oxide synthase from arginine and by reduction of nitrate/nitrite by tissue xanthine oxidoreductase (XOR) or microbiome. Previously, we reported in several mammalian species, including human, that skeletal muscle is a major nitrate reservoir in the body and that nitrate from this reservoir is systemically available and used to generate nitrite and NO. In our recent large animal study, we found that there are similar levels of nitrate stored in bone and skin. In our prior study, skeletal muscle showed a high level of nitrate at 57±39 nmol/g, relative to other tissues, such as liver and plasma at 15±5 nmol/g and 34±19 nmol/g, respectively. Here, we found that the average level of nitrate in the bone is 45±17 nmol/g and in the skin 41±19 nmol/g.Considering that the skeletal muscle, skin and skeleton are three largest organs in mammals, forming about 35-50%, 21% and 14% of body weight, respectively, these results highlight the importance of skeletal muscle as a main nitrate reservoir and the role of skin and bone as new auxiliary nitrate reservoirs. Along with skeletal muscle, the bones and skin likely play an important role in maintaining homeostasis of the nitrate-nitrite-nitric oxide pathway.Also, important from therapeutic point of view, all three organs are well responding to dietary nitrate interventions by increasing their respective nitrate levels, which leads to general increase of systemic and local NO availability and perhaps could be used as one of the ways to increase NO availability in some diseases. This work was supported by intramural NIDDK/NIH grant ZIA DK 025104-15 to Alan N. Schechter. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.