Skip to main content
SpringerLink
Log in

Obstructive Sleep Apnoea and Hypertension: the Role of the Central Nervous System

  • Secondary Hypertension: Nervous System Mechanisms (M Wyss, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of review

Obstructive sleep apnoea (OSA) is associated with both nocturnal and daytime hypertensions which increase cardiovascular morbidity and mortality. It is thought that the repeated episodes of hypoxia and hypercapnia during nocturnal airway obstructions that characterise OSA result in increased sympathetic drive that persists during wakefulness. Although the underlying mechanisms responsible for this hypertension remain to be elucidated, several neural and humoral mechanisms have been proposed and recent evidence suggesting changes in the central nervous system may play a significant role. The purpose of this review is to explore recent evidence of central changes associated with elevated sympathetic drive in individuals with OSA.

Recent findings

Recent human brain imaging investigations and, in particular, combined microneurography recording of resting sympathetic activity with high-resolution functional magnetic resonance imaging have provided some important insights into changes in brain function and anatomy associated with resting sympathetic activity. Functional and anatomical changes occur in OSA, including in regions of the brainstem circuitry known to be responsible for setting resting sympathetic activity. Furthermore, these changes are reversed following continuous positive airway treatment in concert with reductions in resting sympathetic drive.

Summary

These resent findings suggest that the central changes may contribute significantly to the hypertension associated with OSA.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217–39.

    Article  PubMed  Google Scholar 

  2. Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A. Sleep apnea and sleep disruption in obese patients. Arch Intern Med. 1994;154(15):1705–11.

    Article  CAS  PubMed  Google Scholar 

  3. Bearpark H, Elliott L, Grunstein R, et al. Snoring and sleep apnea. A population study in Australian men. Am J Respir Crit Care Med. 1995;151(5):1459–65.

    Article  CAS  PubMed  Google Scholar 

  4. Davies RJ, Crosby J, Prothero A, Stradling JR. Ambulatory blood pressure and left ventricular hypertrophy in subjects with untreated obstructive sleep apnoea and snoring, compared with matched control subjects, and their response to treatment. Clin Sci (Lond). 1994;86(4):417–24.

    Article  CAS  Google Scholar 

  5. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283(14):1829–36.

    Article  CAS  PubMed  Google Scholar 

  6. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84.

    Article  CAS  PubMed  Google Scholar 

  7. Silverberg DS, Oksenberg A, Iaina A. Sleep-related breathing disorders as a major cause of essential hypertension: fact or fiction? Curr Opin Nephrol Hypertens. 1998;7(4):353–7.

    Article  CAS  PubMed  Google Scholar 

  8. Fagard RH, Celis H, Thijs L, et al. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008;51(1):55–61.

    Article  CAS  PubMed  Google Scholar 

  9. Marrone O, Riccobono L, Salvaggio A, Mirabella A, Bonanno A, Bonsignore MR. Catecholamines and blood pressure in obstructive sleep apnea syndrome. Chest. 1993;103(3):722–7.

    Article  CAS  PubMed  Google Scholar 

  10. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96(4):1897–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Elam M, McKenzie D. Macefield V (1985) Mechanisms of sympathoexcitation: single-unit analysis of muscle vasoconstrictor neurons in awake OSAS subjects. J Appl Physiol. 2002;93(1):297–303.

    Article  PubMed  Google Scholar 

  12. Fatouleh R, McKenzie DK, Macefield VG. Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep apnoea. Exp Physiol. 2014;99(10):1288–98.

    Article  PubMed  Google Scholar 

  13. Fatouleh RH, Hammam E, Lundblad LC, et al. Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea. Neuroimage Clin. 2014;6:275–83. A study showing changes in higher brain functional activity associated with resting muscle sympathetic nerve activity in OSA.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lundblad LC, Fatouleh RH, Hammam E, McKenzie DK, Macefield VG, Henderson LA. Brainstem changes associated with increased muscle sympathetic drive in obstructive sleep apnoea. Neuroimage. 2014;103:258–66.

    Article  PubMed  Google Scholar 

  15. Lanfranchi P, Somers VK. Obstructive sleep apnea and vascular disease. Respir Res. 2001;2(6):315–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand. 2003;177(3):385–90.

    Article  CAS  PubMed  Google Scholar 

  17. Narkiewicz K, Montano N, Cogliati C, van de Borne PJ, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation. 1998;98(11):1071–7.

    Article  CAS  PubMed  Google Scholar 

  18. Narkiewicz K, Pesek CA, Kato M, Phillips BG, Davison DE, Somers VK. Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea. Hypertension. 1998;32(6):1039–43.

    Article  CAS  PubMed  Google Scholar 

  19. Frattola A, Parati G, Cuspidi C, Albini F, Mancia G. Prognostic value of 24-hour blood pressure variability. J Hypertens. 1993;11(10):1133–7.

    Article  CAS  PubMed  Google Scholar 

  20. Kleiger RE, Miller JP, Bigger Jr JT, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59(4):256–62.

    Article  CAS  PubMed  Google Scholar 

  21. Fauchier L, Babuty D, Cosnay P, Autret ML, Fauchier JP. Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value. J Am Coll Cardiol. 1997;30(4):1009–14.

    Article  CAS  PubMed  Google Scholar 

  22. Narkiewicz K, Somers VK. Obstructive sleep apnea as a cause of neurogenic hypertension. Curr Hypertens Rep. 1999;1(3):268–73.

    Article  CAS  PubMed  Google Scholar 

  23. Ip MS, Lam B, Chan LY, 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 Med. 2000;162(6):2166–71.

    Article  CAS  PubMed  Google Scholar 

  24. 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(12):1046–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Phillips BG, Narkiewicz K, Pesek CA, Haynes WG, Dyken ME, Somers VK. Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J Hypertens. 1999;17(1):61–6.

    Article  CAS  PubMed  Google Scholar 

  26. Ip MS, Lam KS, Ho C, Tsang KW, Lam W. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest. 2000;118(3):580–6.

    Article  CAS  PubMed  Google Scholar 

  27. Phillips BG, Kato M, Narkiewicz K, Choe I, Somers VK. Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 2000;279(1):H234–7.

    CAS  PubMed  Google Scholar 

  28. Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation. 1998;98(8):772–6.

    Article  CAS  PubMed  Google Scholar 

  29. Narkiewicz K, van de Borne PJ, Pesek CA, Dyken ME, Montano N, Somers VK. Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea. Circulation. 1999;99(9):1183–9.

    Article  CAS  PubMed  Google Scholar 

  30. Dampney RA. Functional organization of central pathways regulating the cardiovascular system. Physiol Rev. 1994;74(2):323–64.

    CAS  PubMed  Google Scholar 

  31. Zhang J, Veasey S. Making sense of oxidative stress in obstructive sleep apnea: mediator or distracter? Front Neurol. 2012;3:179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Y, Veasey SC. Neurobiology and neuropathophysiology of obstructive sleep apnea. Neuromolecular Med. 2012;14(3):168–79.

    Article  CAS  PubMed  Google Scholar 

  33. Harper RM, Macey PM, Henderson LA, et al. fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. J Appl Physiol (1985). 2003;94(4):1583–95.

    Article  Google Scholar 

  34. Henderson LA, Woo MA, Macey PM, et al. Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome. J Appl Physiol (1985). 2003;94(3):1063–74.

    Article  Google Scholar 

  35. Macey KE, Macey PM, Woo MA, et al. Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea. Respir Physiol Neurobiol. 2006;151(1):44–60.

    Article  PubMed  Google Scholar 

  36. Macey PM, Macey KE, Henderson LA, et al. Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea. Respir Physiol Neurobiol. 2003;138(2–3):275–90.

    Article  CAS  PubMed  Google Scholar 

  37. Macey PM, Kumar R, Woo MA, Yan-Go FL, Harper RM. Heart rate responses to autonomic challenges in obstructive sleep apnea. PLoS One. 2013;8(10):e76631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ongur D, An X, Price JL. Prefrontal cortical projections to the hypothalamus in macaque monkeys. J Comp Neurol. 1998;401(4):480–505.

    Article  CAS  PubMed  Google Scholar 

  39. Pool JL, Ransohoff J. Autonomic effects on stimulating rostral portion of cingulate gyri in man. J Neurophysiol. 1949;12(6):385–92.

    CAS  PubMed  Google Scholar 

  40. Critchley HD, Mathias CJ, Josephs O, et al. Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. Brain. 2003;126(Pt 10):2139–52.

    Article  PubMed  Google Scholar 

  41. Sica AL, Greenberg HE, Scharf SM, Ruggiero DA. Immediate-early gene expression in cerebral cortex following exposure to chronic-intermittent hypoxia. Brain Res. 2000;870(1–2):204–10.

    Article  CAS  PubMed  Google Scholar 

  42. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology. 1992;42(9):1727–32.

    Article  CAS  PubMed  Google Scholar 

  43. Cechetto DF, Chen SJ. Subcortical sites mediating sympathetic responses from insular cortex in rats. Am J Physiol. 1990;258(1 Pt 2):R245–55.

    CAS  PubMed  Google Scholar 

  44. Christensen H, Boysen G, Christensen AF, Johannesen HH. Insular lesions, ECG abnormalities, and outcome in acute stroke. J Neurol Neurosurg Psychiatry. 2005;76(2):269–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Colivicchi F, Bassi A, Santini M, Caltagirone C. Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke. Stroke. 2005;36(8):1710–5.

    Article  PubMed  Google Scholar 

  46. Oppenheimer SM, Kedem G, Martin WM. Left-insular cortex lesions perturb cardiac autonomic tone in humans. Clin Auton Res. 1996;6(3):131–40.

    Article  CAS  PubMed  Google Scholar 

  47. Park B, Palomares JA, Woo MA, Kang DW, Macey PM, Yan-Go FL et al. Aberrant insular functional network integrity in patients with obstructive sleep apnea. Sleep. 2016.

  48. Macey PM, Henderson LA, Macey KE, et al. Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;166(10):1382–7.

    Article  PubMed  Google Scholar 

  49. Joo EY, Tae WS, Lee MJ, et al. Reduced brain gray matter concentration in patients with obstructive sleep apnea syndrome. Sleep. 2010;33(2):235–41.

    PubMed  PubMed Central  Google Scholar 

  50. Macey PM, Sarma MK, Nagarajan R, Aysola R, Siegel JM, Harper RM et al. Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex. J Sleep Res. 2016.

  51. Fatouleh RH, Lundblad LC, Macey PM, McKenzie DK, Henderson LA, Macefield VG. Reversal of functional changes in the brain associated with obstructive sleep apnoea following 6 months of CPAP. Neuroimage Clin. 2015;7:799–806.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lundblad LC, Fatouleh RH, McKenzie DK, Macefield VG, Henderson LA. Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation. J Neurophysiol. 2015;114(2):893–901. A study showing both functional and structural changes with brainstem cardiovascular circuitry in OSA that is subsequently restored following 6 months of CPAP treatment.

    Article  PubMed  Google Scholar 

  53. Henderson LA, Fatouleh RH, Lundblad LC, McKenzie DK, Macefield VG. Effects of 12 months continuous positive airway pressure on sympathetic activity related brainstem function and structure in obstructive sleep apnea. Front Neurosci. 2016;10:90.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li YW, Dampney RA. Expression of Fos-like protein in brain following sustained hypertension and hypotension in conscious rabbits. Neuroscience. 1994;61(3):613–34.

    Article  CAS  PubMed  Google Scholar 

  55. Morrison SF, Reis DJ. Responses of sympathetic preganglionic neurons to rostral ventrolateral medullary stimulation. Am J Physiol. 1991;261(5 Pt 2):R1247–56.

    CAS  PubMed  Google Scholar 

  56. Dampney RA. Brain stem mechanisms in the control of arterial pressure. Clin Exp Hypertens. 1981;3(3):379–91.

    Article  CAS  PubMed  Google Scholar 

  57. Saper CB, Loewy AD. Efferent connections of the parabrachial nucleus in the rat. Brain Res. 1980;197(2):291–317.

    Article  CAS  PubMed  Google Scholar 

  58. Loewy AD. Raphe pallidus and raphe obscurus projections to the intermediolateral cell column in the rat. Brain Res. 1981;222(1):129–33.

    Article  CAS  PubMed  Google Scholar 

  59. Hade JS, Mifflin SW, Donta TS, Felder RB. Stimulation of parabrachial neurons elicits a sympathetically mediated pressor response in cats. Am J Physiol. 1988;255(6 Pt 2):H1349–58.

    CAS  PubMed  Google Scholar 

  60. Miyawaki T, Kawamura H, Komatsu K, Yasugi T. Chemical stimulation of the locus coeruleus: inhibitory effects on hemodynamics and renal sympathetic nerve activity. Brain Res. 1991;568(1–2):101–8.

    Article  CAS  PubMed  Google Scholar 

  61. Henderson LA, Keay KA, Bandler R. The ventrolateral periaqueductal gray projects to caudal brainstem depressor regions: a functional-anatomical and physiological study. Neuroscience. 1998;82(1):201–21.

    Article  CAS  PubMed  Google Scholar 

  62. Coleman MJ, Dampney RA. Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus. Am J Physiol. 1995;268(5 Pt 2):R1295–302.

    CAS  PubMed  Google Scholar 

  63. Len WB, Chan JY. Glutamatergic projection to RVLM mediates suppression of reflex bradycardia by parabrachial nucleus. Am J Physiol. 1999;276(5 Pt 2):H1482–92.

    CAS  PubMed  Google Scholar 

  64. Coleman MJ, Dampney RA. Sympathoinhibition evoked from caudal midline medulla is mediated by GABA receptors in rostral VLM. Am J Physiol. 1998;274(2 Pt 2):R318–23.

    CAS  PubMed  Google Scholar 

  65. Amunts K, Schlaug G, Jancke L, et al. Motor cortex and hand motor skills: structural compliance in the human brain. Hum Brain Mapp. 1997;5(3):206–15.

    Article  CAS  PubMed  Google Scholar 

  66. Maguire EA, Gadian DG, Johnsrude IS, et al. Navigation-related structural change in the hippocampi of taxi drivers. Proc Natl Acad Sci U S A. 2000;97(8):4398–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sluming V, Barrick T, Howard M, Cezayirli E, Mayes A, Roberts N. Voxel-based morphometry reveals increased gray matter density in Broca’s area in male symphony orchestra musicians. Neuroimage. 2002;17(3):1613–22.

    Article  PubMed  Google Scholar 

  68. Garcia JH, Yoshida Y, Chen H, et al. Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol. 1993;142(2):623–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Matute C, Domercq M, Sanchez-Gomez MV. Glutamate-mediated glial injury: mechanisms and clinical importance. Glia. 2006;53(2):212–24.

    Article  PubMed  Google Scholar 

  70. Aviles-Reyes RX, Angelo MF, Villarreal A, Rios H, Lazarowski A, Ramos AJ. Intermittent hypoxia during sleep induces reactive gliosis and limited neuronal death in rats: implications for sleep apnea. J Neurochem. 2010;112(4):854–69.

    Article  CAS  PubMed  Google Scholar 

  71. Duru S, Hikmet Firat I, Colak N, Ginis Z, Delibasi T, Ardic S. Serum S100B protein: a useful marker in obstructive sleep apnea syndrome. Neurol Neurochir Pol. 2012;46(5):450–5. A study showing significantly increased plasma levels of a protein associated with astrocytes and possibly calcium waves in OSA subjects.

    CAS  PubMed  Google Scholar 

  72. Ben Achour S, Pascual O. Astrocyte-neuron communication: functional consequences. Neurochem Res. 2012;37(11):2464–73.

    Article  CAS  PubMed  Google Scholar 

  73. Halassa MM, Fellin T, Haydon PG. The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med. 2007;13(2):54–63.

    Article  CAS  PubMed  Google Scholar 

  74. Gourine AV, Kasymov V, Marina N, et al. Astrocytes control breathing through pH-dependent release of ATP. Science. 2010;329(5991):571–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Discipline of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, Australia

    Luke A. Henderson

  2. Department of Anatomy and Histology, F13, University of Sydney, Sydney, Australia

    Luke A. Henderson

  3. School of Medicine, University of Western Sydney, Sydney, Australia

    Vaughan G. Macefield

Authors
  1. Luke A. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vaughan G. Macefield
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luke A. Henderson.

Ethics declarations

Conflict of Interest

Drs. Henderson and Macefield declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Secondary Hypertension: Nervous System Mechanisms

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henderson, L.A., Macefield, V.G. Obstructive Sleep Apnoea and Hypertension: the Role of the Central Nervous System. Curr Hypertens Rep 18, 59 (2016). https://doi.org/10.1007/s11906-016-0665-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-016-0665-2

Keywords

Search

Navigation