Skip to main content
SpringerLink
Log in

Exhaled Nitric Oxide During Exercise

  • Leading Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Endogenously produced nitric oxide (NO) is detectable in the exhaled air of resting humans, and the amount of exhaled NO increases during exercise. It is believed that NO is likely to have an important role in the normal physiological response to exercise. Despite accumulating evidence of exhaled NO during exercise, the effects and relevance of NO to exercise are not yet completely understood. Scientific debate surrounds the site of NO production and the stimuli for production. Resolution of these controversial issues will explain the significance of exhaled NO during exercise.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gustafsson LE, Leone AE, Persson MG, et al. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991; 181: 852–7

    Article  PubMed  CAS  Google Scholar 

  2. Maroun MJ, Mehta S, Turcotte R, et al. Effects of physical conditioning on endogenous nitric oxide output during exercise. J Appl Physiol 1995; 79: 1219–25

    PubMed  CAS  Google Scholar 

  3. Phillips CR, Giraud GD, Holden WE. Exhaled nitric oxide during exercise: site of release and modulation by ventilation and blood flow. J Appl Physiol 1996; 80: 1865–71

    PubMed  CAS  Google Scholar 

  4. Popescu LM, Foril CP, Hinescu M, et al. Nitroglycerin stimulates sarcolemmal Ca2+ extrusion ATPase of coronary smooth muscle cells. Biochem Pharmacol 1985; 34: 1875–9

    Article  Google Scholar 

  5. Schultz KD, Schultz K, Schultz G. Sodium nitroprusside and other smooth muscle relaxants increase cGMP levels in rat ductus deferens. Nature 1977; 265: 750–1

    Article  PubMed  CAS  Google Scholar 

  6. Raeyrnaekers L, Hoffmann F, Casteels R. Cyclic GMP-dependent protein kinase phosphorylates phospholamba in isolated sarcoplasmic reticulum from cardiac and smooth muscle. Biochem J 1988; 252: 269–73

    Google Scholar 

  7. Twort CHC, Van Breemen C. cGMP-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle. Circ Res 1988; 62: 961–4

    Article  PubMed  CAS  Google Scholar 

  8. Furukawa KI, Ohshima N, Tawada-Tata Y, et al. Cyclic GMP stimulates Na+/Ca2+ exchange in vascular smooth muscle cells in primary culture. J Biol Chem 1991; 266: 12337–41

    PubMed  CAS  Google Scholar 

  9. Leone AM, Gustafsson LE, Francis PL, et al. Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation. Biochem Biophys Res Commun 1994; 201: 883–7

    Article  PubMed  CAS  Google Scholar 

  10. Bauer JA, Wald JA, Doran S, et al. Endogenous nitric oxide in expired air: effects of acute exercise in humans. Life Sci 1994; 55: 1903–9

    Article  PubMed  CAS  Google Scholar 

  11. Iwamoto J, Pendergrast DR, Suzuki H, et al. Effect of graded exercise on nitric oxide in expired air in humans. Respir Physiol 1994; 97: 333–45

    Article  PubMed  CAS  Google Scholar 

  12. Chirpaz-Oddou MF, Favre-Juvin A, Flore P, et al. Nitric oxide response in exhaled air during an incremental exhaustive exercise. J Appl Physiol 1997; 82: 1311–8

    PubMed  CAS  Google Scholar 

  13. Persson MG, Wiklund NP, Gustafsson LE. Endogenous nitric oxide in single exhalations and the change during exercise. Am Rev Respir Dis 1993; 148: 1210–4

    PubMed  CAS  Google Scholar 

  14. Pogliaghi S, Krasney JA, Pendergast DR. Effect of gravity on lung exhaled nitric oxide at rest and during exercise. Respir Physiol 1997; 107: 157–64

    Article  PubMed  CAS  Google Scholar 

  15. Matsumoto A, Hirata Y, Momomura S, et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50

    Article  PubMed  CAS  Google Scholar 

  16. Trolin G, Anden T, Hedenstierna G. Nitric oxide (NO) in expired air at rest and during exercise. Acta Physiol Scand 1994; 151: 159–63

    Article  PubMed  CAS  Google Scholar 

  17. Schedin U, Roken BO, Nyman G, et al. Endogenous nitric oxide in the airways of different animal species. Acta Physiol Scand 1997; 41: 1133–41

    CAS  Google Scholar 

  18. Gustafsson LE. Exhaled nitric oxide production in the lung. In: Zapol WM, Bloch KD, editors. Nitric oxide and the lung. New York: Marcel Dekker, 1997: 185–201

    Google Scholar 

  19. Silkoff PE, McClean PA, Slutsky AS, et al. Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am J Respir Crit Care Med 1997; 155: 260–7

    PubMed  CAS  Google Scholar 

  20. Hogman H, Stromberg S, Schedin U, et al. Nitric oxide from the human respiratory tract efficiently quantified by standardised single breath measurements. Acta Physiol Scand 1997; 159: 345–6

    Article  PubMed  CAS  Google Scholar 

  21. Kimberly B, Nejadnik B, Giraud GD, et al. Nasal contribution to exhaled nitric oxide at rest and during breathholding in humans. Am J Respir Crit Care Med 1996; 153: 829–36

    PubMed  CAS  Google Scholar 

  22. Robbins RA, Floreani AA, Von Essen SG, et al. Measurement of exhaled nitric oxide by three different techniques. Am J Respir Crit Care Med 1996; 153: 1631–5

    PubMed  CAS  Google Scholar 

  23. Schedin U, Frostell C, Persson MG, et al. Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans. Acta Physiol Scand 1995; 39: 327–32

    CAS  Google Scholar 

  24. Lundberg JON, Rinder J, Weitzberg E, et al. Heavy physical exercise decreases nitric oxide levels in the nasal airways in humans. Acta Physiol Scand 1997; 159: 51–7

    Article  PubMed  CAS  Google Scholar 

  25. Rinder J. Sensory neuropeptides and nitric oxide in nasal vascular regulation. Acta Physiol Scand 1996; 157: 7–45

    Article  Google Scholar 

  26. Falck B, Aust R, Svanholm H, et al. The effect of physical work on the mucosal blood flow and gas exchange in the human maxillary sinus. Rhinology 1989; 27: 241–50

    PubMed  CAS  Google Scholar 

  27. Ohki M, Hasegawa M, Kurita N, et al. Effects of exercise on nasal blood flow. Acta Otolaryngol 1987; 104: 328–33

    Article  PubMed  CAS  Google Scholar 

  28. Kingwell BA, Sherrard B, Jennings GL, et al. Four weeks of cycle training increases basal production of nitric oxide in the forearm. Am J Physiol 1997; 272: H1070–7

    PubMed  CAS  Google Scholar 

  29. Gilligan DM, Panza JA, Kilcoyne CM, et al. Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation 1994; 90: 2853–8

    Article  PubMed  CAS  Google Scholar 

  30. Sessa WC, Pritchard K, Seyedi N, et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide gene expression. Circ Res 1994; 74: 349–53

    Article  PubMed  CAS  Google Scholar 

  31. Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endothelium- mediated dilation of epicardial coronary artery in dogs. Circ Res 1993; 73: 829–38

    Article  PubMed  CAS  Google Scholar 

  32. Ambring A, Benthin G, Petersson AS, et al. Indirect evidence of increased expression of NO synthase in marathon runners, and upregulation of NO synthase activity during running [abstract]. Circulation 1994; 90: I137

    Google Scholar 

  33. Jungersten L, Ambring A, Wall B, et al. Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans. J Appl Physiol 1997; 82: 760–4

    Article  PubMed  CAS  Google Scholar 

  34. Shen W, Zhang X, Zhao G, et al. Nitric oxide production and NO synthase gene expression contribute to vascular regulation during exercise. Med Sci Sports Exerc 1995; 27: 1125–34

    PubMed  CAS  Google Scholar 

  35. Poveda JJ, Riestra A, Salas E, et al. Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training. Eur J Clin Invest 1997; 27: 967–71

    Article  PubMed  CAS  Google Scholar 

  36. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993; 6: 1368–70

    PubMed  CAS  Google Scholar 

  37. Byrnes CA, Dinarevic S, Busst C, et al. Is nitric oxide in exhaled air produced at airway or alveolar level? Eur Respir J 1997; 10: 1021–5

    Article  PubMed  CAS  Google Scholar 

  38. Shaul PW, North AJ, Wu LC, et al. Endothelial nitric oxide synthase is expressed in cultured bronchiolar epithelium. J Clin Invest 1994; 94: 2231–6

    Article  PubMed  CAS  Google Scholar 

  39. Borland C, Cox Y, Higenbottam T. Measurement of exhaled nitric oxide in man. Thorax 1993; 48: 1160–2

    Article  PubMed  CAS  Google Scholar 

  40. Kharitonov SA, Chung KF, Evans D, et al. Increased exhaled nitric oxide in asthma is mainly derived from the lower respiratory tract. Am J Respir Crit Care Med 1996; 153: 1773–80

    PubMed  CAS  Google Scholar 

  41. Cremona G, Higenbottam T, Takao M, et al. Exhaled nitric oxide in isolated pig lungs. J Appl Physiol 1995; 78: 59–63

    PubMed  CAS  Google Scholar 

  42. Kobzik L, Bredt DS, Lowenstein CJ, et al. Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol 1993; 9: 371–7

    PubMed  CAS  Google Scholar 

  43. Stromberg S, Lormqvist PA, Persson MG, et al. Lung distension and carbon dioxide affect pulmonary nitric oxide formation in the anaesthetized rabbit. Acta Physiol Scand 1997; 159: 59–67

    Article  PubMed  CAS  Google Scholar 

  44. Persson MG, Gustafsson LE, Wiklund NP, et al. Endogenous nitric oxide as probable modulator of pulmonary circulation and hypoxic pressor response in vivo. Acta Physiol Scand 1990; 140: 449–59

    Article  PubMed  CAS  Google Scholar 

  45. Pohl U, Holtz J, Busse R, et al. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986; 8: 27–44

    Article  Google Scholar 

  46. Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1996; 250: H1145–9

    Google Scholar 

  47. Melkumyants AM, Balashov SA, Khayutin VM. Control of arterial lumen by shear stress on endothelium. News Physiol Sci 1995; 10: 204–10

    Google Scholar 

  48. Wilson JR, Kapoor S. Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans. J Appl Physiol 1993; 75: 2740–4

    PubMed  CAS  Google Scholar 

  49. Sumino H, Sato K, Sakamaki T, et al. Decreased basal production of nitric oxide in patients with heart disease. Chest 1998; 113: 317–22

    Article  PubMed  CAS  Google Scholar 

  50. Persson MG, Lonnqvist PA, Gustafsson LE. Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in the air exhaled by rabbits. Anesthesiology 1995; 82: 969–74

    Article  PubMed  CAS  Google Scholar 

  51. Pison U, Lopez FA, Heidelmeyer CF, et al. Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange. J Appl Physiol 1993; 74: 1287–92

    Article  PubMed  CAS  Google Scholar 

  52. Frostell C, Fratacci MD, Wain JC, et al. Inhaled nitric oxide; a selective pulmonary vasodilator reversing hypoxic vasoconstriction. Circulation 1991; 83: 2038–47

    Article  PubMed  CAS  Google Scholar 

  53. Putensen C, Rasanen J, Lopez FA. Improvement in VA/Q distributions during inhalation of nitric oxide in pigs with methacholine- induced bronchoconstriction. Am J Respir Crit Care Med 1995; 151: 116–22

    PubMed  CAS  Google Scholar 

  54. Roger N, Barbera JA, Roca J, et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156: 800–6

    PubMed  CAS  Google Scholar 

  55. Fagan KA, Sato K, Tyler RC, et al. Endothelial nitric oxide synthase (eNOS) knock-out mice develop pulmonary hypertension [abstract]. Circulation 1997; 96: I61

    Article  Google Scholar 

  56. Stamler JS, Loh E, Roddy MA, et al. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 1994; 89: 2035–40

    Article  PubMed  CAS  Google Scholar 

  57. Kharitonov SA, Yates D, Robbins RA, et al. Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994; 343: 133–5

    Article  PubMed  CAS  Google Scholar 

  58. Persson MG, Zetterstrom O, Argenius V, et al. Single-breath oxide measurements in asthmatic patients and smokers. Lancet 1994; 343: 146–7

    Article  PubMed  CAS  Google Scholar 

  59. Hamid Q, Springall DR, Riveros-Moreno V, et al. Induction of nitric oxide synthase in asthma. Lancet 1993; 342: 1510–3

    Article  PubMed  CAS  Google Scholar 

  60. Barnes PJ, Kharitonov SA. Exhaled nitric oxide: a new lung function test. Thorax 1996; 51: 233–7

    Article  PubMed  CAS  Google Scholar 

  61. Dempsey JA, Hanson PG, Henderson KS. Exercise-induced arterial hypoxemia in healthy human subjects at sea level. J Physiol (Lond) 1984; 355: 161–75

    CAS  Google Scholar 

  62. Hopkins SR, McKenzie DC. Hypoxic ventilatory response and arterial desaturation during heavy work. J Appl Physiol 1989; 67: 1119–24

    PubMed  CAS  Google Scholar 

  63. Hopkins SR, McKenzie DC, Schoene RB, et al. Pulmonary gas exchange during exercise in athletes. I: ventilation-perfusion mismatch and diffusion limitation. J Appl Physiol 1994; 77: 912–7

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allan McGavin Sports Medicine Center, The University of British Columbia, Vancouver, British Columbia, Canada

    A. William Sheel & Donald C. McKenzie

  2. Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada

    Jeremy Road

Authors
  1. A. William Sheel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeremy Road
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donald C. McKenzie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. William Sheel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sheel, A.W., Road, J. & McKenzie, D.C. Exhaled Nitric Oxide During Exercise. Sports Med 28, 83–90 (1999). https://doi.org/10.2165/00007256-199928020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-199928020-00003

Keywords

Search

Navigation