Advertisement

Sleep and Breathing

, Volume 7, Issue 2, pp 53–61 | Cite as

Nitric Oxide (NO) and Obstructive Sleep Apnea (OSA)

  • James S. J. Haight
  • Per Gisle Djupesland
Review Article

Abstract

Nitric oxide (NO) and obstructive sleep apnea are inseparable. Obstructive sleep apnea could be described as the intermittent failure to transport the full complement of nasal NO to the lung with each breath. There NO matches perfusion to ventilation. NO is utilized by the efferent pathways that control the unequal, inspiratory battle between the pharyngeal dilators and the closing negative pressures induced by the thoracic musculature. Recurrent cortical arousals are a major short-term complication, and the return to sleep after each arousal uses NO. The long-term complications, namely hypertension, myocardial infarction, and stroke, might be due to the repeated temporary dearth of NO in the tissues, secondary to a lack of oxygen, one of NO’s two essential substrates.

Keywords

Nitric oxide sleep apnea sleep-disordered breathing airway obstruction hypoxia arousals 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kula S, RemmersJE. Anatomy and physiology of upper airway obstruction. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia, PA: WB Saunders; 2000:840–858Google Scholar
  2. 2.
    Krueger JM, Obal Jr F, Fang J, Kubota T, Taishi P. The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 2001;933:211–221Google Scholar
  3. 3.
    Djupesland PG, Chatkin JM, Qian W, HaightJSJ. Nitric oxide in the nasal airway: a new dimension to otorhinolaryngology. Am J Otolaryngol Head Neck Surg 2002;22:19–32Google Scholar
  4. 4.
    Antonin I, Mayo,JC, Sainz RM, et al. Protective effect of melatonin in a chronic experimental model of Parkinson’s disease. Brain Res 2002;943:163–173Google Scholar
  5. 5.
    Cespuglio R, Burlet S, Faradji-Prevautel H. 5-Hydroxy indole compounds and nitric oxide volumetric detection in the rat brain: changes occurring throughout the sleep-wake cycle. J Neural Transm 1998;105(2–3):205–215Google Scholar
  6. 6.
    Pokk P, Vali M. The effect of the nitric oxide synthase inhibitors on the behaviour of the small-platform-stressed mice in the plus-maze test. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:241–247Google Scholar
  7. 7.
    Qian W, DjupeslandPG, Haight JSJ. Unpublished data: 2000Google Scholar
  8. 8.
    Osanai S, Ide H, Yamamoto Y, Nakano H, Kikuchi K. Nitric oxide in sleep apneics Japanese. J Clin Med 2000;58:1665–1670Google Scholar
  9. 9.
    Agusti AG, Barbe F, Togores B. Exhaled nitric oxide in patients with sleep apnea. Sleep 1999;22:231–235Google Scholar
  10. 10.
    Haight JSJ, Djupesland PG, Qian W, et al. Does nasal nitric oxide come from the sinuses?. J Otolaryngol 1999;28:197–204Google Scholar
  11. 11.
    Stamler JS, Loh E, RoddyMA, et al. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 1994;89:2035–2040Google Scholar
  12. 12.
    Blitzer ML, Loh E, RoddyMA, et al. Endothelium derived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxia in humans. J Am Coll Cardiol 1996;28:591–596CrossRefPubMedGoogle Scholar
  13. 13.
    Lundberg JO, Settergren G, Gelinder S, Lundberg JM, AlvingK, Weitzberg E. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand 1996;158:343–347Google Scholar
  14. 14.
    Djupesland PG, Chatkin JM, Qian W, et al. Aerodynamic influences on nasal nitric oxide output measurements. Acta Otolaryngol 1999;119:479–485Google Scholar
  15. 15.
    Cole P. Stability of nasal airflow resistance. Clin Otolaryngol Allied Sci 1989;14:177–182Google Scholar
  16. 16.
    Cole P, HaightJSJ. Posture and the nasal cycle. Ann Otol Rhinol Laryngol 1986;95:233–234Google Scholar
  17. 17.
    Cole P, HaightJSJ. Posture and nasal patency. Am Rev Respir Dis 1984;129:351–354Google Scholar
  18. 18.
    Haight JSJ, Cole P. Topographic anatomy of the pressure points that alter nasal resistance. J Otolaryngol 1986;15(suppl 16):S14–S14Google Scholar
  19. 19.
    Qian W, Sabo R, Ohm M, Haight JSJ, FentonR. Nasal nitric oxide and the nasal cycle. Laryngoscope 2001;111:1603–1607Google Scholar
  20. 20.
    McNicholas WT, Tarlo S, Cole P. Obstructive sleep apnea during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 1982;126:625–628Google Scholar
  21. 21.
    Leznoff A, Haight JSJ, HoffsteinV. Reversible obstructive sleep apnea due to occupational exposure to guar gum dust. Am Rev Respir Dis 1986;133:935–936Google Scholar
  22. 22.
    Djupesland PG, Skatvedt O, BorgersenAK. Dichotomous physiological effects of nocturnal external nasal dilation in heavy snorers: the answer to a rhinologic controversy?. Am J Rhinol 2001;15:95–103Google Scholar
  23. 23.
    Miljeteig H, Savard P, Mateika S, Cole P, Haight JSJ, HoffsteinV. Snoring and nasal resistance during sleep. Laryngoscope 1993;103:918–923Google Scholar
  24. 24.
    Cannon 3rdRO, Schechter AN, Panza JA, et al. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 2001;108:279–287Google Scholar
  25. 25.
    Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, ZapolWM. Inhaled nitric oxide for adult respiratory distress syndrome [comment]. N Engl J Med 1993;328:399–405CrossRefPubMedGoogle Scholar
  26. 26.
    Klinger JR. Inhaled nitric oxide in ARDS. Crit Care Clin 2002;18:45–68Google Scholar
  27. 27.
    Singh S, EvansTW. Nitric oxide the biological mediator of the decade: fact or fiction?. Euro Respir J 1997;10:699–707Google Scholar
  28. 28.
    Jia L, Bonaventura C, Bonaventura J, StamlerJS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996;380:221–226CrossRefPubMedGoogle Scholar
  29. 29.
    Stamler JS, Jia L, EuJP, et al. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 1999;276:2034–2037Google Scholar
  30. 30.
    Rassaf T, Preik M, Kleinbongard P, et al. Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 2002;109:1241–1248Google Scholar
  31. 31.
    Myers JL, Wizorek JJ, Myers AK, et al. Maturation alters the pulmonary arterial response to hypoxia and inhaled nitric oxide in the presence of endothelial dysfunction. J Thorac Cardiovasc Surg 1997;113:270–277Google Scholar
  32. 32.
    Kobzik L, ReidMB, Bredt DS, Stamler JS. Nitric oxide in skeletal muscle. Nature 1994;372:546–548PubMedGoogle Scholar
  33. 33.
    Murrant CL, Woodley NE, Barclay JK. Effect of nitroprusside and endothelium derived products on slow-twitch skeletal muscle function in vitro. Can J Physiol Pharmacol 1994;72:1089–1093Google Scholar
  34. 34.
    Morrison RJ, Miller IIICC, Reid MB. Nitric oxide effects on shortening velocity and power production in the rat diaphragm. J Appl Physiol 1996;80:1065–1069Google Scholar
  35. 35.
    Morrison RJ, Miller IIICC, Reid MB. Nitric oxide effects on force-velocity characteristics of the rat diaphragm. Comp Biochem Physiol 1998;119:203–209Google Scholar
  36. 36.
    Gath I, Closs EI, Godtel-ArmbrustU, et al. Expressed in different structures of guinea-pig skeletal muscle: implications for contractile function. FASEB J 1996;10:1614–1620Google Scholar
  37. 37.
    Reid MB. Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance. Acta Physiol Scand 1998;162:401–409Google Scholar
  38. 38.
    Marshall JM. Roles of adenosine and nitric oxide in skeletal muscle in acute and chronic hypoxia. Adv Exp Med Biol 2001;502:349–363Google Scholar
  39. 39.
    Fitts RH, Balog EM. Effect of intracellular and extracellular ion changes on E-C coupling and skeletal muscle fatigue. Acta Physiol Scand 1996;156:169–181Google Scholar
  40. 40.
    Bruton JD, Lannergren J, Westerblad H. Mechanisms underlying the slow recovery of force after fatigue: importance of intracellular calcium. Acta Physiol Scand 1998;162:285–293Google Scholar
  41. 41.
    Gutierrez C, Qian W, Kendall C, Zamel N, Jenkins D, HaightJSJ. Effect of dietary arginine on exhaled and nasal nitric oxide. Am J Respir Crit Care Med 2000;161:A744–A744Google Scholar
  42. 42.
    Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 2001;64:365–391Google Scholar
  43. 43.
    Blanchard AR, Chaudhary BA. Neuropharmacology of sleep and wakefulness. In: Lee-Chiong TL, Sateira MJ, Carskadon MA eds. Sleep Medicine. Philadelphia, PA; Hanley & Belfus Inc;; 2002:565–574Google Scholar
  44. 44.
    Leonard TO, Lydic R. Pontine nitric oxide modulates acetylcholine release rapid eye movement sleep generation and respiratory rate. J Neurosci 1997;17:774–785Google Scholar
  45. 45.
    Seigel JM. Brainstem mechanisms generating REM sleep. In: Kryger M, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia, PA: WB Saunders;; 2000:112–133Google Scholar
  46. 46.
    Lai YY, Seigel JM. Medullary regions mediating atonia. J Neurosci 1988;8:4790–4796Google Scholar
  47. 47.
    Datta S, PattersonEH, Siwek DF. Endogenous and exogenous nitric oxide in the pedunculo-pontine tegmentum induces sleep. Synapse 1997;27:69–78Google Scholar
  48. 48.
    Lai YY, Seigel JM. Muscle tone suppression and stepping produced by stimulation of midbrain and rostral pontine reticular formation. J Neurosci 1990;10:2727–2738Google Scholar
  49. 49.
    Lai YY, Seigel JM. Ponto-medullary glutamate receptors mediating locomotion and muscle tone suppression. J Neurosci 1991;11:2931–2937Google Scholar
  50. 50.
    Prast H, Tran MH, FischerH, Philippu A. Nitric oxide induced release of acetycholine in the nucleus accumbens: role of cyclic GMP, glutamate and GABA. J Neurochem 1998;71:266–273Google Scholar
  51. 51.
    Kimura T, Yu JG, Edvinsson L, LeeTJF. Cholinergic nitric oxide innervation in cerebral arteries of the cat. Brain Res 1997;773:117–124Google Scholar
  52. 52.
    Bach-y-Rita P. Nonsynaptic diffusion neurotransmission (NDN) in the brain. Neurochem Int 1993;23:297–318Google Scholar
  53. 53.
    Liu X, Miller MJ, Joshi MS, Sadowska-Krowicka H, Clark DA, Lancaster JrJR. Diffusion-limited reaction of free nitric oxide with erythrocytes. J Biol Chem 1998;273:18709–18713Google Scholar
  54. 54.
    Krueger JM, Obal Jr F, Fang J, Kubota T, Taishi P. The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 2001;933:211–221Google Scholar
  55. 55.
    Sippel JM, Giraud GD, Holden WE. Nasal administration of the nitric oxide synthase inhibitor L-NAME induces daytime somnolence. Sleep 1999;22:786–788Google Scholar
  56. 56.
    Cespuglio R, Burlet S, Marinesco S, Robert F, Jouvet M. Volumetric detection of cerebral NO in rats. Variations of the signal throughout the sleep-wakefulness cycle. C R Acad Sci III 1996;319:191–200Google Scholar
  57. 57.
    Kato M, Roberts, Thomson P, et al. Impairment of endothelium dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 2000;102:2607–2610Google Scholar
  58. 58.
    Shepard JrJW, Garrison MW, Grither DA, et al. Relationship of ventricular ectopy to nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease. Am J Med 1995;78:28–34Google Scholar
  59. 59.
    Butkov N. Atlas of Clinical PolysomngraphySynapse Media Inc; 1996Google Scholar
  60. 60.
    Haight JSJ, Qian W. Hypoxia depresses nitric oxide output in the human nasal airway. Laryngoscope 2000;110:429–433Google Scholar
  61. 61.
    Duchna HW, Guilleminault C, StoohsRA, et al. Obstructive sleep apnea syndrome: a cardiovascular risk factor?. Zschr Kardiol 2001;90:568–575Google Scholar
  62. 62.
    Ip MS, Lam B, ChanLY, et al. Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care 2000;162:2166–2171Google Scholar
  63. 63.
    Schulz R, Schmidt D, Blum A, et al. Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea: response to CPAP therapy. Thorax 2000;55:1046–1051CrossRefPubMedGoogle Scholar
  64. 64.
    McQuillan LP, Leung GK, Marsden PA, Kostyk SK, Kourembanas S. Hypoxia inhibits expression of eNOS via transcriptional and post-transcriptional mechanisms. Am J Physiol 1994;267(5 Pt 2):H1921–1927Google Scholar
  65. 65.
    Carlson J, Hedner J, Pettersson A. Increased plasma concentration of ADMA, a naturally occurring nitric oxide synthesis inhibitor, in OSA patients. Am J Respir Crit Care 1997;155:A869–A869Google Scholar
  66. 66.
    Schulz R, Seeger W, Grimminger F. Serum nitrite/nitrate levels in obstructive sleep apnea [letter]. Am J Respir Crit Care 2000;164:1997–1998Google Scholar
  67. 67.
    Lavery CE, Mittleman MA, Cohen MC, et al. No uniform nighttime distribution of acute cardiac events. A possible effect of sleep states. Circulation 1997;96:3321–3327Google Scholar
  68. 68.
    Muller JG, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989;79:733–743PubMedGoogle Scholar
  69. 69.
    Rossi GB, Seccia TM, Nussdorfer GG. Reciprocal regulation of endothelin-1 and nitric oxide: relevance in the physiology and pathology of the cardiovascular system. Int Rev Cytol 2001;209:241–272Google Scholar
  70. 70.
    Gewaltig MT, Kojda G. Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovasc Res 2002;55:250–260Google Scholar
  71. 71.
    Hung J, WithfordEG, Parsons RW, Hillman DR. Association of sleep apnea with myocardial infarction in men. Lancet 1990;336:261–264Google Scholar
  72. 72.
    Koskenvuo M, Kaprio J, Telakivi T, et al. Snoring as a risk factor for ischemic heart disease and stroke in men. Br Med J 1987;294:16–19Google Scholar
  73. 73.
    Ross R. Mechanisms of disease—atheroslerosis—an inflammatory disease. N Engl J Med 1999;340:115–126CrossRefPubMedGoogle Scholar
  74. 74.
    Schwartz SM. Smooth muscle migration in atherosclerosis and restenosis. J Clin Invest 1997;99:2814–2817Google Scholar
  75. 75.
    Scott-Burden T, VanhouttePM. The endothelium as a regulator of vascular smooth muscle proliferation. Circulation 1993;87 (suppl 5):S51–S55Google Scholar
  76. 76.
    Nakaki T, Nakayama M, Kato R. Inhibition of nitric oxide and nitric oxide producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmacol Mol Pharmacol 1990;189:347–353Google Scholar
  77. 77.
    Bolli R. Cardioprotective function of inducible nitric oxide synthesis and role of nitric oxide in myocardial ischaemia and preconditioning: an overview of a decade research. J Mol Cell Cardiol 2001;33:1897–1918Google Scholar
  78. 78.
    Brooks D, HornerRL, Kozar LF, et al. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest 1997;99:106–109Google Scholar
  79. 79.
    Brooks D, HornerRL, Kimoff LF, et al. Effect of obstructive sleep apnea versus sleep fragmentation on responses to airway occlusion. Am J Respir Crit Care Med 1997;155:1609–1617Google Scholar
  80. 80.
    Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746–1752Google Scholar
  81. 81.
    Lavie P, Herer P, Hoffstein V. Obstructive sleep apnea syndrome as a risk factor for hypertension: population study. Br Med J 2000;320:479–482Google Scholar
  82. 82.
    Huang PL, Huang ZH, Mashimo H, et al. Hypertension in mice lacking the egene for endothelial nitric oxide synthase. Nature 1995;377:239–242Google Scholar
  83. 83.
    Kunsch C, MedfordRM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 1999;85:753–766PubMedGoogle Scholar
  84. 84.
    Kojda G, HarrisonDG. Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 1999;43:562–571Google Scholar
  85. 85.
    Massberg S, Sausbier M, Klatt P, et al. Increased adhesion and aggregation of platelets lacking cyclic guanosine 3’-5’-monophosphate kinase I. J Exp Med 1999;189:1255–1263Google Scholar
  86. 86.
    Kubes P, Suzuki M, GrangerDN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 1991;88:4651–4655Google Scholar

Copyright information

© Thieme Medical Publishers, Inc. 2003

Authors and Affiliations

  • James S. J. Haight
    • 1
  • Per Gisle Djupesland
    • 2
  1. 1.Department of Otorhinolaryngology, St. Michael’s HospitalUniversity of TorontoTorontoCanada
  2. 2.OptiNose ASOsloNorway

Personalised recommendations