Dietary nitrate flows and accumulation in pig organs:15N-tracer study

Abstract

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 to nitrite by tissue xanthine oxidoreductase (XOR) and microbiome. Nitrite is then available for reduction to NO by XOR or several heme proteins. Previously we reported that 1) skeletal muscle acts as a body nitrate reservoir, and 2) stored nitrate is systemically, as well as locally used to generate nitrite and NO. Recently, we identified two additional nitrate storage organs - skeleton and skin. At baseline conditions, nitrate concentration in skeleton was 96±63 nmol/g, skeletal muscle 57±39 nmol/g and skin 56±22 nmol/g. For comparison, plasma and liver contained 34±19 nmol/g and 15±5 nmol/g of nitrate, respectively. We used 15N-labeled dose of dietary nitrate to trace its distribution among organs in time. Three hours after nitrate bolus ingestion, total nitrate levels significantly increased in all organs, reaching 221±91 nmol/g in plasma, 126±55 nmol/g in skin, 119±38 nmol/g in skeleton, 100±79 mmol/g in skeletal muscle, and 21±5 nmol/g in liver. As shown by MS, 15N-labeled nitrate distributes in non-uniform way, accumulating largely in skin. As expected, nitrate reductase activity is highest in liver, but also substantial in skin and skeletal muscle, as seen by presence of 15N-labeled nitrite. With consideration of skeletal muscle, skin and skeleton as three largest organs in mammals, these results underline their major 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 and perhaps could be used as one of the ways to increase NO availability. Work supported by NIH internal grant to ANS. This is the full abstract presented at the American Physiology Summit 2024 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.