Distribution of dietary nitrate and its metabolites in rat tissues after 15N-labeled nitrate administration

Ji Won Park, Barbora Piknova, Peter J. Walter, Hongyi Cai, Supranee Upanan, Samantha M. Thomas, Khalid J. Tunau-Spencer, Alan N. Schechter

Research output: Contribution to journalArticlepeer-review


The reduction pathway of nitrate (NO3) and nitrite (NO2) to nitric oxide (NO) contributes to regulating many physiological processes. To examine the rate and extent of dietary nitrate absorption and its reduction to nitrite, we supplemented rat diets with Na15NO3-containing water (1 g/L) and collected plasma, urine and several tissue samples. We found that plasma and urine showed 8.8- and 11.7-fold increases respectively in total nitrate concentrations in 1-day supplementation group compared to control. In tissue samples—gluteus, liver and eyes—we found 1.7-, 2.4- and 4.2-fold increases respectively in 1-day supplementation group. These increases remained similar in 3-day supplementation group. LC–MS/MS analysis showed that the augmented nitrate concentrations were primarily from the exogenously provided 15N-nitrate. Overall nitrite concentrations and percent of 15N-nitrite were also greatly increased in all samples after nitrate supplementation; eye homogenates showed larger increases compared to gluteus and liver. Moreover, genes related to nitrate transport and reduction (Sialin, CLC and XOR) were upregulated after nitrate supplementation for 3 days in muscle (Sialin 2.3-, CLC1 1.3-, CLC3 2.1-, XOR 2.4-fold) and eye (XOR 1.7-fold) homogenates. These results demonstrate that dietary nitrate is quickly absorbed into circulation and tissues, and it can be reduced to nitrite in tissues (and likely to NO) suggesting that nitrate-enriched diets can be an efficient intervention to enhance nitrite and NO bioavailability.

Original languageEnglish
Article number3499
JournalScientific Reports
Issue number1
StatePublished - Dec 2023
Externally publishedYes


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