Nitrate as a source of nitrite and nitric oxide during exercise hyperemia in rat skeletal muscle
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The presence of nitric oxide (NO) synthase enzymes, mainly the NOS1 isoform, in skeletal muscle had been well established; however in the last decade it has been realized that NO may also be produced by reduction of nitrate and tissue nitrite. We have recently shown that rodent skeletal muscle contains unusually high concentrations of nitrate, compared to blood and other tissues, likely produced by oxidation of NOS1-produced NO. In the present study we measured nitrate and nitrite levels in Wistar rat leg tissue before and after acute and chronic exercise of the animals on a treadmill. We found a very large decrease of muscle nitrate levels immediately after exercise accompanied by a transient increase of nitrite levels. A significant decrease in blood nitrate levels accompanied the changes in muscle levels. Using skeletal muscle tissue homogenates we established that xanthine oxidoreductase (XOR) is at least partially responsible for the generation of nitrite and/or NO from nitrate and that this effect is increased by slight lowering of pH and by other processes related to the exercise itself. We hypothesize that the skeletal muscle nitrate reservoir contributes significantly to the generation of nitrite and then, probably via formation of NO, exercise-induced functional hyperemia. A model for these metabolic interconversions in mammals is presented. These reactions could explain the muscle-generated vasodilator causing increased blood flow, with induced contraction, exercise, or hypoxia, postulated more than 100 years ago.
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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 [90]
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References 33 · Cited by 75
- Authors
- Piknova, B., Park, J. W., Kwan (Jeff) Lam, K., & Schechter, A. N.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Piknova, Barbora
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 55-56
- Pages
- 54-61
- ISSN
- 1089-8603 (ISSN-L)
- PMC
- PMC4860042
- OpenAlex
- W2302340018
- Cited by
- 75
- References
- 33
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 12 · 2017: 3 · 2016: 1
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- nitrate, nitrite, exercise hyperemia, skeletal muscle, xanthine oxidoreductase, nitric oxide synthase, NOS1, exercise-induced vasodilation, blood flow, pH, treadmill exercise, hypoxia
- MeSH terms
- Animals, Hyperemia, Male, Nitrates, Nitric Oxide, Nitrites, Physical Conditioning, Animal, Xanthine Dehydrogenase, Rats, Wistar, Muscle, Skeletal
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