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. 2001 Oct;56(10):774–778. doi: 10.1136/thorax.56.10.774

Effects of nitrogen dioxide exposure and ascorbic acid supplementation on exhaled nitric oxide in healthy human subjects

D Chambers 1, J Ayres 1
PMCID: PMC1745935  PMID: 11562516

Abstract

BACKGROUND—Nitric oxide (NO) is detectable in the exhaled breath, is involved in airway defence and inflammation, and probably modulates bronchial smooth muscle tone. Given the sensitivity of nitrogen oxides to local redox conditions, we postulated that exposure to oxidant or antioxidant compounds could alter concentrations of NO in the exhaled breath (eNO). We assessed the effect of nitrogen dioxide (NO2) and ascorbic acid exposure on eNO in healthy human subjects.
METHODS—Ten healthy subjects were randomised to undergo a 20 minute single blind exposure to NO2 (1.5 parts per million) or medical air in a crossover fashion. Exhaled NO and pulmonary function were measured before and for 3 hours after exposure. In a separate double blind crossover study 20 healthy subjects received ascorbic acid 500 mg twice daily or placebo for 2 weeks with a 6 week interim washout. Serum ascorbic acid levels and eNO were measured before and after each supplementation phase.
RESULTS—NO2 induced a decrease of 0.62 (95% CI 0.32 to 0.92) ppb in the mean post-exposure eNO (p<0.01) with no change in forced expiratory volume in 1 second (FEV1). Oral supplementation with ascorbic acid increased the mean serum ascorbic acid concentration by 7.4(95% CI 5.1 to 9.7) µg/ml (63%) but did not alter eNO.
CONCLUSIONS—NO2 exposure causes a decrease in eNO, an effect which may be mediated through changes in epithelial lining fluid redox state or through a direct effect on epithelial cells. In contrast, ascorbic acid does not appear to play a significant role in the metabolism of NO in the epithelial lining fluid.



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Selected References

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  1. Balint B., Donnelly L. E., Hanazawa T., Kharitonov S. A., Barnes P. J. Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke. Thorax. 2001 Jun;56(6):456–461. doi: 10.1136/thorax.56.6.456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. J., Liew F. Y. Nitric oxide and asthmatic inflammation. Immunol Today. 1995 Mar;16(3):128–130. doi: 10.1016/0167-5699(95)80128-6. [DOI] [PubMed] [Google Scholar]
  3. Blomberg A., Krishna M. T., Bocchino V., Biscione G. L., Shute J. K., Kelly F. J., Frew A. J., Holgate S. T., Sandström T. The inflammatory effects of 2 ppm NO2 on the airways of healthy subjects. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):418–424. doi: 10.1164/ajrccm.156.2.9612042. [DOI] [PubMed] [Google Scholar]
  4. Chambers D. C., Ayres J. G. Effect of nebulised L- and D-arginine on exhaled nitric oxide in steroid naive asthma. Thorax. 2001 Aug;56(8):602–606. doi: 10.1136/thorax.56.8.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chambers D. C., Tunnicliffe W. S., Ayres J. G. Acute inhalation of cigarette smoke increases lower respiratory tract nitric oxide concentrations. Thorax. 1998 Aug;53(8):677–679. doi: 10.1136/thx.53.8.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Devalia J. L., Campbell A. M., Sapsford R. J., Rusznak C., Quint D., Godard P., Bousquet J., Davies R. J. Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro. Am J Respir Cell Mol Biol. 1993 Sep;9(3):271–278. doi: 10.1165/ajrcmb/9.3.271. [DOI] [PubMed] [Google Scholar]
  7. Devalia J. L., Sapsford R. J., Cundell D. R., Rusznak C., Campbell A. M., Davies R. J. Human bronchial epithelial cell dysfunction following in vitro exposure to nitrogen dioxide. Eur Respir J. 1993 Oct;6(9):1308–1316. [PubMed] [Google Scholar]
  8. Gaston B., Drazen J. M., Loscalzo J., Stamler J. S. The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):538–551. doi: 10.1164/ajrccm.149.2.7508323. [DOI] [PubMed] [Google Scholar]
  9. Ho L. P., Innes J. A., Greening A. P. Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide. Thorax. 1998 Aug;53(8):680–684. doi: 10.1136/thx.53.8.680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hunt J. F., Fang K., Malik R., Snyder A., Malhotra N., Platts-Mills T. A., Gaston B. Endogenous airway acidification. Implications for asthma pathophysiology. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):694–699. doi: 10.1164/ajrccm.161.3.9911005. [DOI] [PubMed] [Google Scholar]
  11. Jain B., Rubinstein I., Robbins R. A., Leise K. L., Sisson J. H. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun. 1993 Feb 26;191(1):83–88. doi: 10.1006/bbrc.1993.1187. [DOI] [PubMed] [Google Scholar]
  12. Kelly F. J., Blomberg A., Frew A., Holgate S. T., Sandstrom T. Antioxidant kinetics in lung lavage fluid following exposure of humans to nitrogen dioxide. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1700–1705. doi: 10.1164/ajrccm.154.6.8970358. [DOI] [PubMed] [Google Scholar]
  13. Kharitonov S. A., Robbins R. A., Yates D., Keatings V., Barnes P. J. Acute and chronic effects of cigarette smoking on exhaled nitric oxide. Am J Respir Crit Care Med. 1995 Aug;152(2):609–612. doi: 10.1164/ajrccm.152.2.7543345. [DOI] [PubMed] [Google Scholar]
  14. Kharitonov S., Alving K., Barnes P. J. Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur Respir J. 1997 Jul;10(7):1683–1693. doi: 10.1183/09031936.97.10071683. [DOI] [PubMed] [Google Scholar]
  15. Levine M., Conry-Cantilena C., Wang Y., Welch R. W., Washko P. W., Dhariwal K. R., Park J. B., Lazarev A., Graumlich J. F., King J. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704–3709. doi: 10.1073/pnas.93.8.3704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Levine M., Rumsey S. C., Daruwala R., Park J. B., Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999 Apr 21;281(15):1415–1423. doi: 10.1001/jama.281.15.1415. [DOI] [PubMed] [Google Scholar]
  17. Marshall H. E., Stamler J. S. NO waiting to exhale in asthma. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):685–687. doi: 10.1164/ajrccm.161.3.16134. [DOI] [PubMed] [Google Scholar]
  18. Matthews J. N., Altman D. G., Campbell M. J., Royston P. Analysis of serial measurements in medical research. BMJ. 1990 Jan 27;300(6719):230–235. doi: 10.1136/bmj.300.6719.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miura M., Yamauchi H., Ichinose M., Ohuchi Y., Kageyama N., Tomaki M., Endoh N., Shirato K. Impairment of neural nitric oxide-mediated relaxation after antigen exposure in guinea pig airways in vitro. Am J Respir Crit Care Med. 1997 Jul;156(1):217–222. doi: 10.1164/ajrccm.156.1.9606040. [DOI] [PubMed] [Google Scholar]
  20. Mohsenin V. Effect of vitamin C on NO2-induced airway hyperresponsiveness in normal subjects. A randomized double-blind experiment. Am Rev Respir Dis. 1987 Dec;136(6):1408–1411. doi: 10.1164/ajrccm/136.6.1408. [DOI] [PubMed] [Google Scholar]
  21. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  22. Stamler J. S. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994 Sep 23;78(6):931–936. doi: 10.1016/0092-8674(94)90269-0. [DOI] [PubMed] [Google Scholar]
  23. Taddei S., Virdis A., Ghiadoni L., Magagna A., Salvetti A. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1998 Jun 9;97(22):2222–2229. doi: 10.1161/01.cir.97.22.2222. [DOI] [PubMed] [Google Scholar]
  24. Tunnicliffe W. S., Burge P. S., Ayres J. G. Effect of domestic concentrations of nitrogen dioxide on airway responses to inhaled allergen in asthmatic patients. Lancet. 1994 Dec 24;344(8939-8940):1733–1736. doi: 10.1016/s0140-6736(94)92886-x. [DOI] [PubMed] [Google Scholar]
  25. Weitzberg E., Lundberg J. O. Nonenzymatic nitric oxide production in humans. Nitric Oxide. 1998;2(1):1–7. doi: 10.1006/niox.1997.0162. [DOI] [PubMed] [Google Scholar]
  26. Xu A., Vita J. A., Keaney J. F., Jr Ascorbic acid and glutathione modulate the biological activity of S-nitrosoglutathione. Hypertension. 2000 Aug;36(2):291–295. doi: 10.1161/01.hyp.36.2.291. [DOI] [PubMed] [Google Scholar]

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