Dietary nitrate supplementation: Effects on plasma nitrite and pulmonary O2 uptake dynamics during exercise in hypoxia and normoxia

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 307, Issue 7, 2014, Pages R920-R930

  Kelly, James ^a   Vanhatalo, Anni ^a   Bailey, Stephen J ^a   Wylie, Lee J ^a   Tucker, Christopher ^a   List, Stephen ^a   Winyard, Paul G ^b   Jones, Andrew M ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

^b UNIVERSITY OF EXETER MEDICAL SCHOOL   (United Kingdom)

Author keywords

Beetroot juice; Efficiency; Hypoxia; Nitric oxide; Performance

Indexed keywords

GLUCOSE; NITRATE;

ADULT; AIRWAY DYNAMICS; ARTERIAL OXYGEN SATURATION; ARTICLE; BEETROOT; CHEMOLUMINESCENCE; COMPARATIVE STUDY; CROSSOVER PROCEDURE; DIET SUPPLEMENTATION; DOUBLE BLIND PROCEDURE; EXERCISE TEST; EXERCISE TOLERANCE; GLUCOSE BLOOD LEVEL; HEART RATE; HUMAN; HYPOXIA; LEAFY VEGETABLE; MALE; NITRATE SUPPLEMENTATION; NORMAL HUMAN; OXYGEN CONSUMPTION; STEADY STATE; THERAPY EFFECT;

EID: 84907664654     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00068.2014     Document Type: Article

References (68)

1. Allen JD, Stabler T, Kenjale A, Ham KL, Robbins JL, Duscha BD, Dobrosielski DA, Annex BH. Plasma nitrite flux predicts exercise performance in peripheral arterial disease after 3 months of exercise training. Free Radic Biol Med 49: 1138–1144, 2010.
2. Amann JA, Calbet M. Convective oxygen transport and fatigue. J Appl Physiol 104: 861–870, 2008.
3. Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AM. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol 109: 135–148, 2010.
4. 2 cost of sub-maximal exercise and enhances exercise tolerance in humans. J Appl Physiol 107: 1144–1155, 2009.
5. Bescós R, Ferrer-Roca V, Galilea PA, Roig A, Drobnic F, Sureda A, Martorell M, Cordova A, Tur JA, Pons A. Sodium nitrate supplementation does not enhance performance of endurance athletes. Med Sci Sports Exerc 44: 2400–2409, 2012.
6. O2 peak in endurance athletes. Med Sci Sports Exerc 43: 1979–1986, 2011.
7. Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith S, Golden M, McKenzie H. Stomach NO synthesis. Nature 368: 502, 1994.
8. 2 uptake kinetics and im-poroves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate. Am J Physiol Regul Integr Comp Physiol 305: R1441–R1450, 2013.
9. Brown GC. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504: 46–57, 2001.
10. Brown GC, Borutaite V. Nitric oxide, cytochrome c and mitochondria. Biochem Soc Symp 66: 17–25, 1999.
11. Bryan NS. Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free Radic Biol Med 41: 691–701, 2006.
12. Casey DP, Madery BD, Curry TB, Eisenach JH, Wilkins BW, Joyner MJ. Nitric oxide contributes to the augmented vasodilation during hy-poxic exercise. J Physiol 588: 373–385, 2010.
13. Castello PR, David PS, McClure T, Crook Z, Poyton RO. Mitochon-drial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signalling in eukaryotes. Cell Metab 3: 277–287, 2006.
14. Cermak NM, Gibala MJ, van Loon LJ. Nitrate supplementation’s improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exerc Metab 22: 64–71, 2012.
15. Curtis E, Hsu LL, Noguchi AC, Geary L, Shiva S. Oxygen regulates tissue nitrite metabolism. Antioxid Redox Signal 17: 951–961, 2012.
16. Dalsgaard T, Simonsen U, Fago A. Nitrite-dependant vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities. Am J Physiol Heart Circ Physiol 292: H3072-H3078, 2007.
17. Dejam A, Hunter CJ, Schechter AN, Gladwin MT. Emerging role of nitrite in human biology. Blood Cells Mol Dis 32: 423–429, 2004.
18. 2 utilization. J Appl Physiol 103: 771–778, 2007.
19. Dreissigacker U, Wendt M, Wittke T, Tsikas D, Maassen N. Positive correlation between plasma nitrite and performance during high-intensive exercise but not oxidative stress in healthy men. Nitric Oxide 23: 128-135, 2010.
20. Dufour SP, Patel RP, Brandon A, Teng X, Pearson J, Barker H, Ali L, Yuen AHY, Smolenski RT, González-Alonso J. Erythrocyte-dependent regulation of human skeletal muscle blood flow: role of varied oxyhemoglobin and exercise on nitrite, S-nitrosohemoglobin, and ATP. Am J Physiol Heart Circ Physiol 299: H1936-H1946, 2010.
21. Duncan C, Dougall H, Johnston P, Green S, Brogan R, Smith L, Golden M, Benjamin N. Chemical generation of nitric oxide in the mouth from the entero-salivary circulation of dietary nitrate. Nat Med 1: 546-551, 1995.
22. Ellis CG, Goldman D, Hanson M, Stephenson AH, Milkovich S, Benlamri A, Ellsworth ML, Sprague RS. Defects in oxygen supply to skeletal muscle of prediabetic ZDF rats. Am J Physiol Heart Circ Physiol 298: H1661-H1670, 2010.
23. Ferguson SK, Hirai DM, Copp SW, Holdsworth CT, Allen JD, Jones AM, Musch TI, Poole DC. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats. J Physiol 591: 547-557, 2013.
24. Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 29: 463-487, 2004.
25. Fish JE, Matouk CC, Yeboah E, Bevan SC, Khan M, Patil K, Ohh M, Marsden PA. Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase. J Biol Chem 282: 15652-15666, 2007.
26. Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Wac-lawiw MA, Panza JA, Ognibene FP, Cannon RO. Role of circulating nitrite on S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci USA 97: 11482-11487, 2000.
27. Govoni M, Jansson EA, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide 19: 333-337, 2008.
28. 2+] and contractile force in mouse fast-twitch muscle. J Physiol 590: 3575-3583, 2012.
29. Hughson RL, Kowalchuk JM. Kinetics of oxygen uptake for submaxi-mal exercise in hyperoxia, normoxia, and hypoxia. Can J Appl Physiol 20: 198-210, 1995.
30. Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE. Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: Comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 90: 8103-8107, 1993.
31. Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman Arghandawi S F, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic nitrate supplementation lowers blood pressure in humans: Role for nitrite-derived NO. Hypertension 56: 274-281, 2010.
32. Kelly J, Fulford J, Vanhatalo A, Blackwell JR, French O, Bailey SJ, Gilchrist M, Winyard PG, Jones AM. Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults. Am J Physiol Regul Integr Comp Physiol 304: R73-R83, 2013.
33. Kelly J, Vanhatalo A, Wilkerson DP, Wylie LJ, Jones AM. Effects of nitrate on the power-duration relationship for severe-intensity exercise. Med Sci Sports Exerc 45: 1798-1806, 2013.
34. Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol 110: 1582-1591, 2011.
35. Keszler A, Piknova B, Schechter AN, Hogg N. The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem 283: 9615-9622, 2008.
36. Lamarra N, Whipp BJ, Ward SA, Wasserman K. Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics. J Appl Physiol 62: 2003–2012, 1987.
37. Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AM. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc 43: 1125–1131, 2011.
38. 2 cost of walking and running: a placebo-controlled study. J Appl Physiol 110: 591–600, 2011.
39. Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab 13: 149–159, 2011.
40. Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med 48: 342–347, 2010.
41. Larsen FJ, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf) 191: 59–66, 2007.
42. Larsen FJ, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E. Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 355: 2792–2793, 2006.
43. Lauer T, Kleinbongard P, Kelm M. Indexes of NO bioavailability in human blood. News Physiol Sci 17: 251–255, 2002.
44. Leuenberger UA, Johnson D, Loomis J, Gray KS, Maclean DA. Venous but not skeletal muscle interstitial nitric oxide is increased during hypobaric hypoxia. Eur J Appl Physiol 102: 457–461, 2008.
45. Levett DZ, Fernandez BO, Riley HL, Martin DS, Mitchell K, Leck-strom CA, Ince C, Whipp BJ, Mythen MG, Montgomery HE, Grocott MP, Feelisch M. The role of nitrogen oxides in humans adaptation to hypoxia. Sci Rep 109: 1–7, 2011.
46. Linnarsson D, Karlsson J, Fagraeus L, Saltin B. Muscle metabolites and oxygen deficit with exercise in hypoxia and hyperoxia. J Appl Physiol 36: 399–402, 1974.
47. Lundberg JO, Carlström M, Larsen FJ, Weitzberg E. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc Res 89: 525–532, 2011.
48. Lundberg JO, Weitzberg E. NO-synthase independent NO generation in mammals. Biochem Biophys Res Commun 396: 39–45, 2010.
49. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7: 156–167, 2008.
50. Masschelein E, Van Thienen R, Wang X, Van Schepdael A, Thomis M, Hespel P. Dietary nitrate improves muscle but not cerebral oxygen-ation status during exercise in hypoxia. J Appl Physiol 113: 736–745, 2012.
51. Muggeridge DJ, Howe CF, Spendiff O, Pedlar C, James PE, Easton C. A single dose of beetroot juice enhances cycling performance in simulated altitude. Med Sci Sports Exerc 46: 143–150, 2014.
52. Ostergaard L, Stankevicius E, Andersen MR, Eskilden-Helmond Y, Ledet T, Mulvany MJ, Simonsen U. Diminished NO release in chronic hypoxic endothelial cells. Am J Physiol Heart Circ Physiol 293: H2894–H2903, 2007.
53. Poveda JJ, Riestra A, Sals E, Cagigas ML, Lopez-somoza C, Amado JA, Berrazueta JR. Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training. Eur J Clin Invest 27: 967–971, 1997.
54. Rassaf T, Laur T, Heiss C, Balzer J, Mangold S, Leyendecker T, Rottler J, Drexhage C, Meyer C, Kelm M. Nitric oxide synthase-derived plasma nitrite predicts exercise capacity. Br J Sports Med 41: 669–673, 2007.
55. 2 consumption in trained human skeletal muscle. J Appl Physiol 87: 325–331, 1999.
56. Rossiter HB, Ward Ward SA, Kowalchuk JM, Howe FA, Griffths JR, Whipp BJ. Effects of prior exercise on oxygen uptake and phosphocre-atine kinetics during high-intensity knee-extension exercise in humans. J Physiol 537: 291–303, 2001.
57. Scheuermann BW, Bell C, Paterson DH, Barstow TJ, Kowalcuk JM. Oxygen uptake kinetics for moderate exercise are speeded in older humans by prior heavy exercise. J Appl Physiol 92: 609–616, 2002.
58. Shaul PW, Wells LB, Horning KM. Acute and prolonged hypoxia attenuate endothelial nitric oxide production in rat pulmonary arteries by different mechanisms. J Cardiovasc Pharmacol 22: 819–827, 1993.
59. Springer C, Barstow TJ, Wasserman K, Cooper DM. Oxygen uptake and heart rate responses during hypoxic exercise in children and adults. Med Sci Sports Exerc 23: 71–79, 1991.
60. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 81: 209–237, 2001.
61. Totzeck M, Hendgen-Cotta UB, Rammos C, Frommke LM, Knack-stedt C, Predel HG, Kelm M, Rassaf T. Higher endogenous nitrite levels are associated with superior exercise capacity in highly trained athletes. Nitric Oxide 27: 75–81, 2012.
62. Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol 299: R1121–R1131, 2010.
63. 2 cost or exercise tolerance. Eur J Appl Physiol 113: 1805–19, 2013.
64. Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol 589: 5517–5528, 2011.
65. Whipp BJ, Wasserman K. Oxygen uptake kinetics for various intensities of constant-load work. J Appl Physiol 33: 351–356, 1972.
66. Wilkerson DP, Hayward GM, Bailey SJ, Vanhatalo A, Blackwell JR, Jones AM. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists. Eur J Appl Physiol 112: 4127–4134, 2012.
67. Wylie LJ, Kelly J, Bailey SJ, Blackwell JR, Skiba PF, Winyard PG, Jeukendrup AE, Vanhatalo A, Jones AM. Beetroot juice and exercise: pharmacodynamics and dose-response relationships. J Appl Physiol 115: 325–336, 2013.
68. Wylie LJ, Mohr M, Krustrup P, Jackman SR, Ermidis G, Kelly J, Black MI, Bailey SJ, Vanhatalo A, Jones AM. Dietary nitrate supplementation improves team sport-specific intense intermittent exercise performance. Eur J Appl Physiol 113: 1673–1684, 2013.