Journal of Molecular Neuroscience

, Volume 21, Issue 1, pp 57–63 | Cite as

Plasma levels of nitric oxide and L-arginine in sleep apnea patients

Effects of nCPAP treatment
  • Lena Lavie
  • Aya Hefetz
  • Rafael Luboshitzky
  • Peretz Lavie
Article

Abstract

Sleep apnea syndrome has been shown to be associated with decreased levels of circulating nitric oxide (NO) after waking up from sleep. In this study we investigated overnight plasma concentrations of NO in sleep apnea patients before and after nasal continuous positive airway pressure (nCPAP) treatment and the effects of nCPAP on morning levels of L-arginine. In experiment 1, NO concentrations measured hourly during sleep were found to be significantly lower in a group of eight sleep apnea patients in comparison with six age-similar snorers and six normal young adults. In experiment 2, overnight NO concentrations were compared in 5 sleep apnea patients before and 9.3±3.9 mo after treatment with nCPAP. A significant increase in NO concentrations was found in four out of five patients, and a significant increase in L-arginine was found in all five patients after treatment. In experiment 3, removal of nCPAP for a single night in seven sleep apnea patients caused a significant decrease in morning levels of NO and L-arginine. These results demonstrate that sleep apnea is associated with a chronic state of diminished circulating NO concentrations that can be ameliorated by nCPAP treatment.

Index Entries

Nitric oxide sleep apnea nCPAP L-arginine 

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References

  1. Ahren C., Jungersten L., and Sandberg T. (1999) Plasma nitrate as an index of nitric oxide formation in patients with acute infectious disease. Scand. J. Infect. Dis. 31, 405–407.PubMedCrossRefGoogle Scholar
  2. Backman J. S. and Koppenol W. H. (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am. J. Physiol. 271, C1421-C1437.Google Scholar
  3. Barcelo A., Miralles C., Barbe F., Vila M., Pons S., and Agusti A. G. (2000) Abnormal lipid peroxidation in patients with sleep apnoea. Eur. Respir. J. 16, 644–647.PubMedCrossRefGoogle Scholar
  4. Carlson J., Hedner J., and Patterson A. (1997) Increased plasma concentration of ADMA a naturally occurring nitric oxide synthesis inhibitor in OSA patients. Am. J. Respir. Crit. Care Med. 155, A869.Google Scholar
  5. Casino P. R., Kilcoyne C. M., Quyyuni A. A., Hoeg J. M., and Panza J. A. (1994) Investigation of decreased availability of nitric oxide precursor as the mechanism responsible for impaired endothelium-dependent vasodilation in hypercholesterolemic patients. J. Am. Coll. Cardiol. 23, 844–850.PubMedCrossRefGoogle Scholar
  6. Chin K., Nakamura T., Shimzu K., Mishima M., Nakamura T., Miyasaka M., and Ohi M. (2000) Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome. Am. J. Med. 109, 562–567.PubMedCrossRefGoogle Scholar
  7. Cooke J. P. and Dzau V. J. (1997) Nitric oxide synthase: role in the genesis of vascular disease. Annu. Rev. Med. 48, 489–509.PubMedCrossRefGoogle Scholar
  8. Dyugovskaya L., Lavie P., and Lavie L. (2002) Increased adhesion molecule expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am. J. Respir. Crit. Care Med. 165, 934–939.PubMedGoogle Scholar
  9. El-Solh A. A., Mador M. J., Sikka P., Dhillon R. S., Amsterdam D., and Grant B. J. (2002) Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest 121, 1541–1547.PubMedCrossRefGoogle Scholar
  10. Faller D. V. (1999) Endothelial cell responses to hypoxic stress. Clin. Exp. Pharmacol. Physiol. 26, 74–84.PubMedCrossRefGoogle Scholar
  11. Grisham M. B., Granger D. N., and Lefer D. J. (1998) Modulation of leukocyte-endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease. Free Radic. Biol. Med. 25, 404–433.PubMedCrossRefGoogle Scholar
  12. Hoffmann A., Gloe T., and Pohl U. (2001) Hypoxia-induced upregulation of eNOS gene expression is redoxsensitive: a comparison between hypoxia and inhibitors of cell metabolism. J. Cell Physiol. 188, 33–44.PubMedCrossRefGoogle Scholar
  13. Ip M. S., Lam B., Chan L. Y., Zheng L., Tsang K. W., Fung P. C. and Lam W. K. (2000) Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am. J. Respir. Crit. Care Med. 162, 2166–2171.PubMedGoogle Scholar
  14. Kato M., Roberts-Thomson P., Phillips B. G., Haynes W. G., Winnicki M., Accurso V., and Somers V. K. (2000) Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102, 2607–2610.PubMedGoogle Scholar
  15. Kelm M. (1999) Nitric oxide metabolism and breakdown. Biochem. Biophys. Acta 1411, 273–289.PubMedCrossRefGoogle Scholar
  16. Knowles R. G. and Moncada S. (1994) Nitric oxide synthases in mammals. Biochem J. 298, 249–258.PubMedGoogle Scholar
  17. Kraiczi H., Caidahl K., Samuelsson A., Peker Y., and Hedner J. (2001) Impairment of vascular endothelial function and left ventricular filling: association with the severity of apnea-induced hypoxemia during sleep. Chest 119, 1085–1091.PubMedCrossRefGoogle Scholar
  18. Kubo S. H., Rector T. S., Bank A. J., Williams R. E., and Heifetz S. M. (1991) Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation 84, 1589–1596.PubMedGoogle Scholar
  19. Kugiyama K., Yasue H., Okumura K., et al. (1996) Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina. Circulation 94, 266–271.PubMedGoogle Scholar
  20. Lavie L. (2003) Obstructive sleep apnea—an oxidative stress disorder. Sleep Med. Rev. 7, 35–51.PubMedCrossRefGoogle Scholar
  21. Lavie P., Herer P., and Hoffstein V. (2000) Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. Br. Med. J. 320, 479–482.CrossRefGoogle Scholar
  22. Lavie L., Perelman A., and Lavie P. (2001) Plasma homocysteine levels in obstructive sleep apnea: association with cardiovascular morbidity. Chest 120, 900–908.PubMedCrossRefGoogle Scholar
  23. Levine G. N., Frei B., Koulouris S. N., Gerhard M. D., Keaney J. F., Jr., and Vita J. A. (1996) Ascorbic acid reverses end othelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93, 1107–1113.PubMedGoogle Scholar
  24. Lieberman E. H., Gerhard M. D., Uehata A., et al. (1996) Flow-induced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease. Am. J. Cardiol. 78, 1210–1214.PubMedCrossRefGoogle Scholar
  25. Lin K. Y., Asagami T., Tsao P. S., et al. (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106, 987–992.PubMedCrossRefGoogle Scholar
  26. Malhotra A. and White D. P. (2002) Obstructive sleep apnoea. Lancet 360, 237–245.PubMedCrossRefGoogle Scholar
  27. McQuillan L. P., Leung G. K., Marsden P. A., Kostyk S. K., and Kourembanas S. (1994) Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am. J. Physiol. 267, H1921-H1927.PubMedGoogle Scholar
  28. Mooe T., Rabben T., Wiklund U., et al. (1996) Sleep-disordered breathing in men with coronary artery disease. Chest 109, 659–663.PubMedGoogle Scholar
  29. Nathan C. and Xie Q. W. (1994) Nitric oxide synthases: roles tolls and controls. Cell 78, 915–918.PubMedCrossRefGoogle Scholar
  30. Node K., Kitakaze M., Yoshikawa H., Kosaka H., and Hori M. (1997) Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension. Hypertension 30, 405–408.PubMedGoogle Scholar
  31. Ohga E., Nagase T., Tomita T., Teramoto S., Matsuse T., Katayama H., and Ouchi Y. (1999) Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J. Appl. Physiol. 87, 10–14.PubMedGoogle Scholar
  32. Panza J. A., Quyyuni A. A., Brush J. E., Jr., and Epstein S. E. (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N. Engl. J. Med. 323, 22–27.PubMedCrossRefGoogle Scholar
  33. Peled N., Abinader E. G., Pillar G., et al. (1999) Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment. J. Am. Coll. Cardiol. 15, 1744–1749.CrossRefGoogle Scholar
  34. Peppard P. E., Young T., Palta M., et al. (2000) Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl. J. Med. 342, 1738–1784.CrossRefGoogle Scholar
  35. Pernow J. and Wang Q. D. (1999) The role of the l-arginine/nitric oxide pathway in myocardial ischaemic and reperfusion injury. Acta Physiol. Scand. 167, 151–159.PubMedCrossRefGoogle Scholar
  36. Phelan M. W. and Faller D. V. (1996) Hypoxia decreases constitutive nitric oxide synthase transcript and protein in culture. J. Cell Physiol. 167, 469–476.PubMedCrossRefGoogle Scholar
  37. Piacentini L. and Karliner J. S. (1999) Altered gene expression during hypoxia and reoxygenation of the heart. Pharmacol. Ther. 83, 21–37.PubMedCrossRefGoogle Scholar
  38. Salvemini D., de Nucci G., Gryglewski R. J., and Vane J. R. (1989) Human neutrophils and mononuclear cells inhibit platlet aggregation by releasing a nitric oxide-like factor. Proc. Natl. Acad. Sci. U. S. A. 86, 6328–6332.PubMedCrossRefGoogle Scholar
  39. Schulz R., Mahmoudi S., Hattar K., et al. (2000a) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 162, 566–570.PubMedGoogle Scholar
  40. Schulz R., Schmidt D., Blum A., Lopes-Ribeiro X., Lucke C., Mayer K., et al. (2000b) Decreased plasma levels of nitric oxide derivative in obstructive sleep apnoea: response to nCPAP therapy. Thorax 55, 1046–1051.PubMedCrossRefGoogle Scholar
  41. Tanaka S., Yashiro A., Nakashima Y., Nanri H., Ikeda M., and Kuroiwa A. (1997) Plasma nitrite/nitrate level is correlated with plasma low-density lipoprotein cholesterol level. Clin. Cardiol. 20, 361–365.PubMedCrossRefGoogle Scholar
  42. Tannenbaum S. R. (1979) Nitrate and nitrite: origin in humans. Science 205, 1333–1335.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Lena Lavie
    • 1
  • Aya Hefetz
    • 1
  • Rafael Luboshitzky
    • 2
  • Peretz Lavie
    • 3
  1. 1.Unit of Anatomy and Cell Biology, Faculty of MedicineTechnion—Israel Institute of TechnologyHaifaIsrael
  2. 2.Haemek Medical CenterEndocrine InstituteAfulaIsrael
  3. 3.Sleep Laboratory, Bruce Rappaport Faculty of Medicine, Technion-IITHaifaIsrael

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