Human skeletal muscle nitrate store: influence of dietary nitrate supplementation and exercise
Wylie LJ, Park JW, Vanhatalo A, Kadach S, Black MI, Stoyanov Z, Schechter AN, Jones AM, Piknova B
The Journal of physiology · 92 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Mechanisms only
- Intake measured by
- Not stated
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- Biotechnology and Biological Sciences Research Council
- Government
- Intramural NIH HHS
- Grants
- Biotechnology and Biological Sciences Research Council (BB/S020632/1); National Institutes of Health (Z99 DK999999); Biotechnology and Biological Sciences Research Council (BB/S020632/1)
Based on 3 listed funder(s).
Publication
- Published
- 2019-07-27 · J Physiol · vol. 597 · issue 23 · pp. 5565–5576
- Publisher
- Wiley
- Cited
- 112 citations · more than 98% of similar papers · 7.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 55 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Nitric Oxide and Endothelin Effects · Exercise and Physiological Responses · Cardiovascular and exercise physiology
- Keywords
- Nitrate, Nitrite, Skeletal muscle, Nitric oxide, Chemistry, Internal medicine, Biochemistry, Endocrinology, Biology, Medicine
- MeSH
- muscle, skeletal, lung, humans, nitrates, nitrites, xanthine dehydrogenase, organic anion transporters, symporters, exercise, oxygen consumption, dietary supplements, adolescent, adult, female, male, young adult
9 authors
From GB, US
- Lee J. WylieUniversity of Exeter
- Ji Won ParkNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Anni VanhataloUniversity of Exeter
- Stefan KadachUniversity of Exeter
- Matthew I. BlackUniversity of Exeter
- Zdravko StoyanovUniversity of Exeter
Abstract
Key points
Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions. We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise. In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high-intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO. We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism.
Abstract
Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise-induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4-fold and ∼29-fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19-fold) and muscle (∼5-fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise-induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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