Effect of dietary nitrate levels on nitrate fluxes in rat skeletal muscle and liver
Open accessAbstract
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.
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Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle and plasma.
“Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle [88,89,90,91] and plasma [53,64,92], and are associated with positive physiological effects [41,64,74,93] that facilitate a greater capacity for muscular work [51,53,59] and/or improved muscle contractile efficiency (i.e., a lower high-energy phosphate cost of force production) [51,94].”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [88]
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References 17 · Cited by 63
- Authors
- Gilliard, C. N., Lam, J. K., Cassel, K. S., Park, J. W., Schechter, A. N., & Piknova, B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Piknova, Barbora
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 75
- Pages
- 1-7
- ISSN
- 1089-8603 (ISSN-L)
- PMC
- PMC5860979
- OpenAlex
- W2794369712
- Cited by
- 63
- References
- 17
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 10 · 2018: 4
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 DK999999)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- dietary nitrate, nitrate starvation, nitrate flux, nitrate storage, nitrate transport, nitric oxide synthase, muscle oxygenation, functional hyperemia, physical activity
- MeSH terms
- Animals, Diet, Liver, Nitrates, Nitrites, Rats, Wistar, Muscle, Skeletal
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