Skip to main content
SpringerLink
Log in

Luminal Nitric Oxide in the Upper Airways: Implications for Local and Distal Sites of Action

  • Chapter
Nitric Oxide in Pulmonary Processes

Part of the book series: Respiratory Pharmacology and Pharmacotherapy ((RPP))

  • 86 Accesses

Abstract

The nose has probably developed primarily to serve as a protection barrier for the lower airways and lungs. The sense of smell is also located in the nose, but may not be vital for the human species. The well-known protective functions of the nose are heating, humidification and filtration of inhaled air. Recently, other protective and regulating functions pertaining to the nasal airways and the paranasal sinuses have been proposed, which involve high nitric oxide (NO) production in the paranasal sinus mucosa. Because this NO can travel with the airstream during inhalation it may play a physiological role not only in the sinuses themselves but also in other parts of the respiratory tract, including the lungs.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Archer S (1992) Measurement of nitric oxide in biological models. FASEB J 7: 349–360

    Google Scholar 

  2. Alving K, Weitzberg E, Lundberg JM (1993) Increased amount of nitric oxide in exhaled air of asthmatics. Eur Resp J 6: 1368–1370

    CAS  Google Scholar 

  3. Lundberg JON, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM, Alving K (1994) Primarily nasal origin of exhaled nitric oxide and absence in Kartagener’s syndrome. Eur Resp J 7: 1501–1504

    Article  CAS  Google Scholar 

  4. Kimberly B, Nejadnik B, Giraud GD, Holden WE (1996) Nasal contribution to exhaled nitric oxide at rest and during breathholding in humans. Am J Respir Crit Care Med 153: 829–836

    PubMed  CAS  Google Scholar 

  5. Imada M, Iwamoto J, Nonaka S, Kobayashi Y, Unno T (1996) Measurement of nitric oxide in human nasal airway. Eur Resp J 9: 556–559

    Article  CAS  Google Scholar 

  6. Rinder J, Lundberg JON, Änggård A, Alving K, Lundberg JM (1996) Effects of topical nasal decongestants, L-arginine and nitric oxide synthase inhibition, on nasal cavity nitric oxide levels and nasal cavity comume in man Am J Rhinol 10: 399–408

    Google Scholar 

  7. Lundberg JON, Rinder J, Weitzberg E, Alving K, Lundberg JM (1997) Heavy physical exercise decreases nitric oxide levels in the nasal airways in humans. Acta Physiol Scand 159: 51–57

    Article  PubMed  CAS  Google Scholar 

  8. Lundberg JON, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Änggård A et al (1995) High nitric oxide production in paranasal sinuses. Nature Med 1: 370–373

    Article  PubMed  CAS  Google Scholar 

  9. Lundberg JON, Hellström P, Lundberg JM, Alving K (1994) Greatly increased luminal nitric oxide in ulcerative colitis. Lancet 344: 1673–1674

    Article  PubMed  CAS  Google Scholar 

  10. Lundberg JON, Ehren I, Jansson 0, Adolfson J, Lundberg JM, Weitzberg E et al (1996) Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. Urology 48: 700–702

    Article  PubMed  CAS  Google Scholar 

  11. Gustaffson LE, Leone AM, Persson MG, Wiklund NP, Moncada S (1991) Endogenous nitric oxide is present in exhaled air of rabbits, guinea-pigs and humans. Biochem Biophys Res Comm 181: 852–857

    Article  Google Scholar 

  12. Borland C, Cox Y, Higenbottam T (1993) Measurement of exhaled nitric oxide in man. Thorax 48: 1160–1162

    Article  PubMed  CAS  Google Scholar 

  13. Persson MG, Wiklund NP, Gustafsson LE (1993) Endogenous nitric oxide in single exhalations and the change during exercise. Am Rev Resp Dis 148: 1210–1214

    PubMed  CAS  Google Scholar 

  14. Gerlach H, Rossaint R, Pappert D, Knorr M, Falke KJ (1994) Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx. Lancet 343: 518–519

    Article  PubMed  CAS  Google Scholar 

  15. Schedin U, Frostell C, Persson MG, Jakobsson J, Andersson G, Gustafsson LE (1995) Contribution from the upper and lower airways to exhaled endogenous nitric oxide in humans Acta Anaesthesiol Scand 39: 327–332

    Article  PubMed  CAS  Google Scholar 

  16. Munch C, Monchi M, Fierobe L, Brunet F, Dhainaut JF, Tuan Dinh-Xuan A (1994) Absence of nitric oxide in airways of ventilated patients. Lancet 343: 1232–1233

    Article  PubMed  CAS  Google Scholar 

  17. Hardy JG, Lee SW, Wilson CG (1985) Intranasal drug delivery by spray and drops. J Pharmaceut Pharmacol 37: 294–297

    Article  CAS  Google Scholar 

  18. Lundberg JON, Rinder J, Weitzberg E, Lundberg JM, Alving K (1994) Nasally exhaled nitric oxide in humans originates mainly in the paranasal sinuses. Acta Physiol Scand 152: 431–432

    Article  PubMed  CAS  Google Scholar 

  19. Trolin G, Anden T, Hedenstierna G (1994) Nitric oxide in expired air at rest and during exercise. Acta Physiol Scand 151: 159–163

    Article  PubMed  CAS  Google Scholar 

  20. Schedin U, Norman M, Gustafsson LE, Herin P, Frostell C (1996) Endogenous nitric oxide in the upper airways of healthy newborn infants. Pediatr Res 40: 148–151

    Article  PubMed  CAS  Google Scholar 

  21. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC et al (1993) Molecular cloning and expression of inducible nitric oxide synthase from hepatocytes. Proc Nail Acad Sci USA 90: 3491–3495

    Article  CAS  Google Scholar 

  22. Charles IG, Palmer RM, Hickery MS, Bayliss MT, Chubb AP, Hall VS et al (1993) Cloning characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Nail Acad Sci USA 90: 11419–11423

    Article  CAS  Google Scholar 

  23. Knowles RG, Moncada S (1994) Nitric oxide snytheses in mammals. Biochem J 298: 249–258

    PubMed  CAS  Google Scholar 

  24. Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FBJM, Erzurum SC (1995) Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci USA 92: 7809–7813

    Article  CAS  Google Scholar 

  25. Kobzik L, Bredt DS, Lowenstein CJ, Drazen J, Gaston B, Sugarbaker D et al (1993) Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am JRespir Cell Mol Biol 9: 371–377

    CAS  Google Scholar 

  26. Springall DR, Mason NA, Redington AE, Meng Q-H, Howarth PH, Polak JM (1996) Inducible nitric oxide synthase is upregulated in nasal epithelium in perennial allergic rhinitis. Am JRespir Crit Care Med 153: A800

    Google Scholar 

  27. Hamid Q, Springall DR, Riveros-Moreno V, Chanez P, Howarth P, Redington A et al (1993) Induction of nitric oxide synthase in asthma. Lancet 342: 1510–1513

    Article  PubMed  CAS  Google Scholar 

  28. Lundberg JON, Weitzberg E, Rinder J, Rudehill A, Janssen 0, Wiklund NP et al (1996) Calcium-independent and steroid-resistant nitric oxide synthase activity in human paranasal sinus mucosa. Eur Resp J 9: 1344–1347

    Article  CAS  Google Scholar 

  29. Xu W, Charles IG, Liu L, Koni PA, Moncada S, Emson P (1995) Molecular genetic analysis of the duplication of human inducible nitric oxide synthase (NOS-2) sequences. Biochem Biophys Res Comm 212: 466–472

    Article  PubMed  CAS  Google Scholar 

  30. Douglas JS, Stitt JT, DuBois AB (1995) Nasal and lung nitric oxide production in human and animals: Effect of endotoxin. Am JRespir Crit Care Med 151: A44

    Google Scholar 

  31. Schedin U, Frostell C, Gustafsson LE (1995) Nitric oxide occurs in high concentrations in monkey upper airways. Acta Physiol Scand 155: 473–474

    Article  PubMed  CAS  Google Scholar 

  32. Lewandowski K, Busch T, Lewandowski M, Keske U, Gerlach U, Falke KJ (1996) Evidence of nitric oxide in the exhaled gas of Asian elephants (Elephas maximus). Respir Physiol 106: 91–98

    Article  PubMed  CAS  Google Scholar 

  33. Eissa NT, Strauss AJ, Haggerty CM, Choo EK, Chu SC, Moss J (1996) Alternative splicing of human inducible nitric oxide synthase mRNA: tissue-specific regulation and induction by cytokines. J Biol Chem 271: 27184–27187

    Article  PubMed  CAS  Google Scholar 

  34. Ringheim GE, Pan J (1995) Particulate and soluble isoforms of the inducible nitric oxide synthase are distinguishable at the amino terminus in RAW 264.7 macrophage cells. Biochem Biophys Res Comm 210: 711–716

    Article  PubMed  CAS  Google Scholar 

  35. Sakai M, Sawada T, Nishimura T, Nagatsu I (1996) Expression of nitric oxide syntheses in the mouse and human nasal mucosa. Acta Histochem Cytochem 29: 177–179

    Article  CAS  Google Scholar 

  36. Furukawa K, Harrison DG, Saleh D, Shennib H, Chagnon FP, Giaid A (1996) Expression of nitric oxide synthase in the human nasal mucosa. Am JRespir Grit Care Med 153: 847–850

    CAS  Google Scholar 

  37. Wink DA, Mims RW, Darbyshire JF, Christodoulou D, Hanbauer I, Cox GW et al (1994) Reaction kinetics for nitrosylation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates in the NO/02reaction. Chem Res Toxicol 7: 519–525

    Article  PubMed  CAS  Google Scholar 

  38. Cantin AM, North SL, Hubbard RC, Crystal RG (1987) Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol 63: 152–157

    PubMed  CAS  Google Scholar 

  39. Testa B, Mesolella M, Testa D, Giuliano A, Costa G, Marione F et al (1995) Glutath one in the upper respiratory tract. Anno Oto Rhinol Latyngol 104: 117–119

    CAS  Google Scholar 

  40. Borland CDR, Higenbottam TW (1989) A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide. Eur Resp J 2: 56–63

    CAS  Google Scholar 

  41. Ji X, Hollocher TC (1989) Nitrite reductase of Escherichia coli as a NO-producing nitrite reductase. Biochem Arch 5: 61–66

    CAS  Google Scholar 

  42. Dillon WC, Hampl V, Shultz PJ, Rubins JB, Archer SL (1996) Origins of breath nitric oxide in humans. Chest 110: 930–938

    Article  PubMed  CAS  Google Scholar 

  43. Zetterquist W, Pedroletti C, Lundberg JON, Alving K (1999) Salivary contribution to exhaled nitric oxide. Eur Resp J 13: 327–333

    Article  CAS  Google Scholar 

  44. Lundberg JON, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35: 1543–1546

    Article  PubMed  CAS  Google Scholar 

  45. Springall DR, Meng Q-H, Redington A, Howarth PH, Evans TJ, Polak JM (1995) Inducible nitric oxide in asthmatic airway epithelium is reduced by corticosteroid therapy. Am JRespir Crit Care Med 151: A833

    Google Scholar 

  46. Kharitonov SA, Yates DH, Barnes PJ (1996) Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am JRespir Crit Care Med 153: 454–457

    CAS  Google Scholar 

  47. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ (1994) Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343: 133–135

    Article  PubMed  CAS  Google Scholar 

  48. Lundberg JON, Nordvall SL, Weitzberg E, Kollberg H, Alving K (1996) Exhaled nitric oxide in paediatric asthma and cystic fibrosis. Arch Dis Child 75: 323–326

    Article  PubMed  CAS  Google Scholar 

  49. Kharitonov SA, Rajakulasingam K, O’Connor B, Durham SR, Barnes PJ (1997) Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids. J Allergy Clin Immunol 99: 58–64

    PubMed  CAS  Google Scholar 

  50. Sato K, Sumino H, Sakamaki T, Sakamoto H, Nakamura T, Ono Z et al (1996) Lack of inhibitory effect of dexamethasone on exhalation of nitric oxide by healthy humans. Internal Med 35: 356–361

    Article  CAS  Google Scholar 

  51. Ohki M, Hasegawa M, Kurita N, Watanabe I (1987) Effects of exercise on nasal resistance and nasal blood flow. Acta Otolaryngol 104: 328–333

    Article  PubMed  CAS  Google Scholar 

  52. Falck B, Aust R, Svanholm H, Backlund L (1989) The effect of physical work on the muco-sal blood flow and gas exchange in the human maxillary sinus. Rhinology 27: 241–250

    PubMed  CAS  Google Scholar 

  53. Akerlund A, Bende M, Arfors K-E, Intaglietta M (1993) Effect of oxymetazolin on nasal and sinus mucosal blood flow in the rabbit as measured with laser-Doppler flowmetry. Ann Otol Rhinol Laryngol 102: 123–126

    PubMed  CAS  Google Scholar 

  54. Kumlien J, Schiratzki H (1985) The vascular arrangement of the sinus mucosa — a study in rabbits. Acta Otolaryngol 99: 122–132

    Article  PubMed  CAS  Google Scholar 

  55. Rinder J, Lundberg JON, Weitzberg E, Lundberg JM, Alving K (1995) Nitric oxide in human nasal airways decreases during exercise. Endothelium 3: S82

    Google Scholar 

  56. Phillips CR, Giraud GD, Holden WE (1996) Exhaled nitric oxide during exercise: site of release and modulation by ventilation and blood flow. J Appl Physiol 80: 1865–1871

    PubMed  CAS  Google Scholar 

  57. Iwamoto J, Pendergast DR, Suzuki H, Krasney JA (1994) Effect of graded exercise on nitric oxide in expired air in humans. Respir Physiol 97: 333–345

    Article  PubMed  CAS  Google Scholar 

  58. Silkoff PE, Mcclean PA, Slutsky AS, Furlott HG, Hoffstein E, Wakita S et al (1997) Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am JRespir Crit Care Med 155: 260–267

    CAS  Google Scholar 

  59. Nathan CF, Hibbs Jr J (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3: 65–70

    Article  PubMed  CAS  Google Scholar 

  60. Croen KD (1993) Evidence for an antiviral effect of nitric oxide. Inhibition of Herpes Simplex type I replication. J Clin Invest 91: 2446–2452

    Article  PubMed  CAS  Google Scholar 

  61. Mancinelli RL, McKay CP (1983) Effects of nitric oxide and nitrogen dioxide on bacterial growth. Appl Environ Microbiol 46: 198–202

    PubMed  CAS  Google Scholar 

  62. Lundberg JON, Nordvall SL, Weitzberg E, Kollberg H, Alving K (1995) Exhaled nitric oxide in paediatric asthma and cystic fibrosis. Endothelium 3: S113

    Article  Google Scholar 

  63. Lindberg S, Cervin A, Runer T (1997) Low levels of nasal nitric oxide (NO) correlate to impaired mucociliary function in the upper airways. Acta Otolaryngol 117: 728–734

    Article  PubMed  CAS  Google Scholar 

  64. Jain B, Rubinstein L, Robbins RA, Leise KL, Sisson JH (1993) Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Comm 191: 83–88

    Article  PubMed  CAS  Google Scholar 

  65. Runer T, Lindberg S (1998) Effects of nitric oxide on blood flow and mucociliary activity in the human nose. Ann Otol Rhinol Latyngol 107: 40–46

    CAS  Google Scholar 

  66. Rossi OVJ, Pirila T, Laitinen J, Huhti E (1994) Sinus aspirates and radiographic abnormalities in severe attacks of asthma. Int Arch Allergy Immunol 103: 209–213

    Article  PubMed  CAS  Google Scholar 

  67. Baraldi E, Azzolin NM, Biban P, Zacchello F (1997) Effect of antibiotic therapy on nasal nitric oxide concentration in children with acute sinusitis. Am J Respir Crit Care Med 155: 1680–1683

    PubMed  CAS  Google Scholar 

  68. Lindberg S, Cervin A, Runer T (1997) Nitric oxide (NO) production in the upper airways is decreased in chronic sinusitis. Acta Otolaryngol 117: 113–117

    Article  PubMed  CAS  Google Scholar 

  69. Ferguson EA, Eccles R (1996) Changes in nasal nitric oxide concentration associated with symptoms of common cold and treatment with a topical nasal decongestant. Br J Clin Pharmacol 42: 657P

    Google Scholar 

  70. Kharitonov SA, Yates DH, Barnes PJ (1995) Increased nitric oxide in exhaled air of normal subjects with upper respiratory tract infections. Eur Resp J 8: 295–297

    Article  CAS  Google Scholar 

  71. Arnal J-F, Didier A, Rami J, M’Rini C, Charlet J-P, Serrano E et al (1997) Nasal nitric oxide is increased in allergic rhinitis. Clin Exp Allergy 27: 358–362

    Article  PubMed  CAS  Google Scholar 

  72. Flak TA, Goldman WE (1996) Autotoxicity of nitric oxide in airway disease. Am J Respir Crit Care Med 154: S202–S206

    PubMed  CAS  Google Scholar 

  73. Wink DA, Hanbauer I, Laval F, Cook JA, Krishna MC, Mitchell JB (1994) Nitric oxide protects against the cytotoxic effects of reactive oxygen species. Ann New York Acad Sci 738: 265–278

    Article  CAS  Google Scholar 

  74. Dear JW, Scadding GK, Foreman JC (1996) Reduction by NG-nitro-L-arginine methyl ester (L-NAME) of antigen-induced nasal airway plasma extravasation in human subjects in vivo. Br J Pharmacol 116: 1720–1722

    Google Scholar 

  75. Erjefalt JS, Erjefalt I, Sundler F, Persson CG (1994) Mucosal nitric oxide may tonically suppress airways plasma exudation. Am J Respir Crit Care Med 150: 227–232

    PubMed  CAS  Google Scholar 

  76. Frostell C, Fratacci M-D, Wain JC, Jones R, Zapol WM (1991) Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83: 2038–2047

    Article  PubMed  CAS  Google Scholar 

  77. Frostell CG, Blomqvist H, Hedenstierna G, Lundberg JM, Zapol WM (1993) Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilatation. Anesthesiology 78: 427–435

    Article  PubMed  CAS  Google Scholar 

  78. Puybasset L, Rouby J, Mourgeon E, Stewart T, Cluzel P, Arthaud M et al (1994) Inhaled nitric oxide in acute respiratory failure: dose-response curves. Intensive Care Med 20: 319–327

    Article  PubMed  CAS  Google Scholar 

  79. Lundberg JON, Lundberg JM, Settergren G, Alving K, Weitzberg E (1995) Nitric oxide, produced in the upper airways, may act in an “aerocrine” fashion to enhance pulmonary oxygen uptake in humans. Acta Physiol Scand 155: 467–468

    Article  PubMed  CAS  Google Scholar 

  80. Lundberg JON, Settergren G, Gelinder S, Lundberg JM, Alving K, Weitzberg E (1996) Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand 158: 343–347

    Article  PubMed  CAS  Google Scholar 

  81. Alving K, Fornhem C, Lundberg JM (1993) Pulmonary effects of endogenous and exogenous nitric oxide in the pig: relation to cigarette smoke inhalation. Br J Pharmacol 110: 739–746

    Article  PubMed  CAS  Google Scholar 

  82. Miller OI, Tang SF, Keech A, Celermajer DS (1995) Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 346: 51–52

    Article  PubMed  CAS  Google Scholar 

  83. Kharitonov SA, Alving K, Barnes PJ (1997) Exhaled and nasal nitric oxide measurements: Recommendations. The European Respiratory Society Task Force. Eur Resp J 10: 1683–1693

    Article  CAS  Google Scholar 

  84. Amal J-F, Flores P, Rami J, Murris-Espin M, Bremont F, Pasto I, Aguilla M, Serrano E, Didier A (1999). Nasal nitric oxide concentration in paranasal sinus inflammatory diseases. Eur Resp J 13: 307–312

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden

    Kjell Alving & Jon O. N. Lundberg

  2. Department of Surgical Sciences, Karolinska Hospital, S-171 76, Stockholm, Sweden

    Johan Rinder & Eddie Weitzberg

Authors
  1. Kjell Alving
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jon O. N. Lundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Johan Rinder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eddie Weitzberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmacology Department, RhĂ´ne-Poulenc Rorer Research & Development, Rainham Road South, Dagenham, Essex, RM 10 7XS, UK

    Maria G. Belvisi

  2. Unit of Critical Care Medicine Imperial College Medical School, Royal Brompton Hospital, Sidney Street, London, SW3 6NP, UK

    Jane A. Mitchell

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Basel AG

About this chapter

Cite this chapter

Alving, K., Lundberg, J.O.N., Rinder, J., Weitzberg, E. (2000). Luminal Nitric Oxide in the Upper Airways: Implications for Local and Distal Sites of Action. In: Belvisi, M.G., Mitchell, J.A. (eds) Nitric Oxide in Pulmonary Processes. Respiratory Pharmacology and Pharmacotherapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8474-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8474-7_10

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9582-8

  • Online ISBN: 978-3-0348-8474-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation