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Endogenous Nitric Oxide Formation in the Respiratory System

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Role of Nitric Oxide in Sepsis and ADRS

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICM,volume 24))

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Abstract

Synthesis of nitric oxide (NO) derived from L-arginine is known to occur in a number of tissues. NO is believed to exert regulatory functions in the circulatory, nervous and immune systems [1,2]. In the respiratory system, NO is known to modulate vascular tone and has been suggested to modulate the pulmonary hypoxic pressor response in vitro and in vivo [3,4]. Administration of NO synthase inhibitors have been found to cause hypoxia in anesthetized rabbits [4] and to interfere with the normal vascular adaptation at birth in a sheep model [5]. Early studies showed that NO could be formed in rat lung homogenates, but also that the formation was markedly smaller than in other tissues, and mainly derived from calcium-independent (inducible) NO synthesis (iNOS) [6]. It was therefore important to elucidate whether NO was actually formed in lungs in vivo, and how NO formation might be affected by various challenges such as hypoxia or allergen challenge. The discovery of NO in exhaled air [7] has made it possible to directly monitor NO formation in the respiratory system, and we will presently focus mainly on knowledge obtained from this method.

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References

  1. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  2. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pahway. N Engl J Med 329: 2002–2012

    Article  PubMed  CAS  Google Scholar 

  3. Archer SL, Tolins JP, Raij L, Weir EK (1989) Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium-derived relaxing factor. Bio- chem Biophys Res Commun 164:1198–1205

    Article  CAS  Google Scholar 

  4. Persson MG, Gustafsson LE, Wiklund NP, Moncada S, Hedqvist P (1990) Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo. Acta Physiol Scand 140:449–457

    Article  PubMed  CAS  Google Scholar 

  5. Abman SH, Chatfield BA, Hall SL, McMurtry IF (1990) Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth. Am J Physiol 259: H1921-H1927

    PubMed  CAS  Google Scholar 

  6. Palacios M, Knowles RG, Moncada S (1992) Enhancers of nonspecific immunity induce nitric oxide synthase: Induction does not correlate with toxicity or adjuvancy. Eur J Immunol 22:2303–2307

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Leone AM, Gustafsson LE, Francis PL, Persson MG, Wiklund NP, Moncada S (1994) Nitric oxide is present in exhaled breath in humans: Direct GcMs confirmation. Biochem Biophys Res Commun 201:883–887

    Article  PubMed  CAS  Google Scholar 

  9. Persson MG, Midtvedt T, Leone AM, Gustafsson LE (1994) Ca2+- and Ca2+-in- dependent exhaled nitric oxide, presence in germ-free animals, and inhibition by argi- nine analogues. Eur J Pharmacol 264:13–20

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  11. Moncada S (1992) The 1991 Ulf von Euler lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand 145:201–227

    Article  PubMed  CAS  Google Scholar 

  12. Schmidt HHHW, Gagne GD, Nakane M, Pollock JS, Miller MF, Murad F (1992) Map** of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem 40:1439–1456

    Article  PubMed  CAS  Google Scholar 

  13. Fischer AP, Mundel P, Mayer B, Preissler U, Philippin B, Kummer W (1993) Nitric oxide synthase in guinea pig lower airway innervation. Neurosci Lett 149:157–160

    Article  PubMed  CAS  Google Scholar 

  14. Kobzik L, Bredt DS, Lowenstein CJ, et al (1993) Nitric oxide synthase in human and rat lung: Immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol 9:371–377

    PubMed  CAS  Google Scholar 

  15. Grozdanovic Z, Bruning G, Baumgarten HG (1994) Nitric oxide — a novel autonomic neurotransmitter. Acta Anat 150:16–24

    Article  PubMed  CAS  Google Scholar 

  16. Asano K, Chee CB, Gaston B, et al (1994) Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc Natl Acad Sci USA 91:10089–10093

    Article  PubMed  CAS  Google Scholar 

  17. Robbins RA, Barnes PJ, Springall DR, et al (1994) Expression of inducible nitric oxide in human lung epithelial cells. Biochem Biophys Res Commun 203:209–218

    Article  PubMed  CAS  Google Scholar 

  18. Schedin U, Norman M, Gustafsson LE, Herin P, Frostell C (1995) High endogenous nitric oxide in the upper airways of healthy new-born infants. Br J Anaesth (In press)

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Persson MG, Kalze’n H, Gustafsson LE (1994) Oxygen or low concentrations of nitric oxide reverse pulmonary vasoconstriction induced by nitric oxide synthesis inhibition in rabbits. Acta Physiol Scand 150:405–411

    Article  PubMed  CAS  Google Scholar 

  22. Sprague RS, Thiemermann C, Vane JR (1992) Endogenous endothelium-derived relaxing factor opposes hypoxic pulmonary vasoconstriction and supports blood flow to hypoxic alveoli in anesthetized rabbits. Proc Natl Acad Sci USA 89:8711–8715

    Article  PubMed  CAS  Google Scholar 

  23. Youngson C, Nurse C, Yeger H, Cutz E (1993) Oxygen sensing in airway chemorecep- tors. Nature 365:153–155

    Article  PubMed  CAS  Google Scholar 

  24. Kourembanas S, McQuillan LP, Leung GK, Faller DV (1993) Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. J Clin Invest 92:99–104

    Article  PubMed  CAS  Google Scholar 

  25. Persson MG, Lonnqvist PA, Gustafsson LE (1995) Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits. Anesthesiology 82 (In press)

    Google Scholar 

  26. Kinsella JP, McQueston J A, Rosenberg A A, Abman SH (1992) Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation. Am J Physiol 263: H875-H880

    PubMed  CAS  Google Scholar 

  27. Stewart TE, Valenza F, Ribeiro SP, et al (1995) Increased NO in exhaled gas as an early marker of lung inflammation in a model of sepsis. Crit Care Med (Suppl 23): A170 (Abst)

    Google Scholar 

  28. Li CG, Rand MJ (1991) Evidence that part of the NANC relaxant response of guinea- pig trachea to electrical field stimulation is mediated by NO. Br J Pharmacol 102:91–94

    PubMed  CAS  Google Scholar 

  29. Belvisi MG, Stretton CD, Yacoub M, Barnes PJ (1992) Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans. Eur J Pharmacol 210:221–222

    Article  PubMed  CAS  Google Scholar 

  30. Dupuy PM, Shore SA, Drazen JM, Frostell C, Hill WA, Zapol WM (1992) Bronchodilator action of inhaled nitric oxide in guinea pigs. J Clin Invest 90:421–428

    Article  PubMed  CAS  Google Scholar 

  31. Högman M, Frostell C, Arnberg H, Hedenstierna G (1993) Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit. Eur Resp J 6: 177–180

    Google Scholar 

  32. Persson MG, Gustafsson LE (1993) Allergen-induced airway obstruction in guinea- pigs is associated with changes in nitric oxide levels in exhaled air. Acta Physiol Scand 149:461–466 Endogenous Nitric Oxide Formation in the Respiratory System 307

    Article  PubMed  CAS  Google Scholar 

  33. Persson MG, Friberg SG, Hedqvist P, Gustafsson LE (1993) Endogenous nitric oxide counteracts antigen-induced bronchoconstriction. Eur J Pharmacol 249: R7-R8

    Article  PubMed  CAS  Google Scholar 

  34. Nijkamp FP, Van der Linde HJ, Folkerts G (1993) Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. Am Rev Respir Dis 148:727–734

    Article  PubMed  CAS  Google Scholar 

  35. Persson MG, Zetterström O, Agrenius V, Ihre E, Gustafsson LE (1994) Single-breath nitric oxide measurements in asthmatic patients and smokers. Lancet 343:146–147

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  37. 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 

  38. Persson MG, Friberg SG, Gustafsson LE, Hedqvist P (1995) Endogenous nitric oxide promotes patent airways and counteracts allergen-induced bronchoconstriction. Br J Pharmacol (In press)

    Google Scholar 

  39. Högman M, Frostell CG, Hedenström H, Hedenstierna G (1993) Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 148:1474–1478

    Article  PubMed  Google Scholar 

  40. 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 

  41. 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 

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

    Article  CAS  Google Scholar 

  43. Schedin U, Frostell C, Persson MG, Jakobsson J, Andersson G, Gustafsson LE (1995) Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans. Acta Anaesthesiol Scand (In press)

    Google Scholar 

  44. Persson MG, Agvald P, Gustafsson LE (1994) Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo. Br J Pharmacol 111: 825–828

    PubMed  CAS  Google Scholar 

  45. Cederqvist B, Persson MG, Gustafsson LE (1994) Direct demonstration of NO formation in vivo from organic nitrites and nitrates, and correlation to effects on blood pressure and to in vitro effects. Biochem Pharmacol 47:1047–1053

    Article  PubMed  CAS  Google Scholar 

  46. Husain M, Adrie C, Ichinose F, Kavosi M, Zapol WM (1994) Exhaled nitric oxide as a marker for organic nitrate tolerance. Circulation 89:2498–2502

    PubMed  CAS  Google Scholar 

  47. Persson MG, Gustafsson LE (1992) Ethanol can inhibit nitric oxide formation. Eur J Pharmacol 224:99–100

    Article  PubMed  CAS  Google Scholar 

  48. Persson MG, Cederqvist B, Wiklund CU, Gustafsson LE (1994) Ethanol causes decrements in airway excretion of endogenous nitric oxide in humans. Eur J Pharmacol 270:273–278

    PubMed  CAS  Google Scholar 

  49. Bauer JA, Wald JA, Doran S, Soda D (1994) Endogenous nitric oxide in expired air: Effects of acute exercise in humans. Life Sci 55:1903–1909

    Article  PubMed  CAS  Google Scholar 

  50. 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 

  51. Cremona G, Higenbottam T, Borland C, Mist B (1994) Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion. QJM 87:547–551

    PubMed  CAS  Google Scholar 

  52. Jain B, Rubinstein I, Robbins RA, Leise KL, Sisson JH (1993) Nitric oxide modulates ciliary activity in airway epithelium. Am Rev Respir Dis 147 (Suppl): A937 (Abst)

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. L. E. Gustafsson
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  2. P. A. Lönnqvist
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  3. M. G. Persson
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Editor information

Editors and Affiliations

  1. Department of Surgery, Beth Israel Hospital, 330 Brookline Avenue, 02215, Boston, MA, USA

    M. P. Fink

  2. Department of Anesthesiology and Intensive Care, Lariboisière University Hospital, 2 rue Ambroise Paré, 75475, Paris Cedex 10, France

    Didier Payen

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© 1995 Springer-Verlag Berlin Heidelberg

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Gustafsson, L.E., Lönnqvist, P.A., Persson, M.G. (1995). Endogenous Nitric Oxide Formation in the Respiratory System. In: Fink, M.P., Payen, D. (eds) Role of Nitric Oxide in Sepsis and ADRS. Update in Intensive Care and Emergency Medicine, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79920-4_19

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  • DOI: https://doi.org/10.1007/978-3-642-79920-4_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79922-8

  • Online ISBN: 978-3-642-79920-4

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