Crucial Role of the Carotid Body Chemoreceptors on the Development of High Arterial Blood Pressure During Chronic Intermittent Hypoxia

  • Rodrigo IturriagaEmail author
  • David C. Andrade
  • Rodrigo Del Rio
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)


Exposure to chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, produces autonomic and cardiorespirartory alterations, and leads to systemic hypertension. These alterations are associated with enhanced carotid body (CB) chemosensory and ventilatory hypoxic reflexes and a decrease baroreflex (BRS) efficiency. The aim of this study was to determine the therapeutic effect of CB ablation on the elevated arterial blood pressure, the reduced BRS and the potentiated ventilatory response induced by CIH in conscious rats. Arterial blood pressure (BP) was continuous measured by telemetry in male Sprague-Dawley rats exposed to CIH (5 % O2, 12 times/h, and 8 h/day). After 21 days of CIH, the CBs were selectively cryodestroyed, and rats were kept one more week in CIH. Ventilatory responses to hypoxia were assessed by whole body plethysmography and spontaneous BRS measured by the sequence method. Exposure to CIH produces hypertension, increased the chemoreflex ventilatory hypoxic responses, and decreased BRS. The ablation of the CBs normalized the elevated BP, and the altered ventilatory response and BRS. Present results suggest that the CB play a crucial role in the development of high arterial pressure and autonomic alterations induced by CIH.


Obstructive sleep apnea Carotid body Intermittent hypoxia Chemoreflex Baroreflex 



This work was supported by grant 1100405 from the National Fund for Scientific and Technological Development of Chile (FONDECYT) and the project Puente 28/2014 of the VRI-PUC.


  1. Del Rio R, Moya EA, Iturriaga R (2010) Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link. Eur Respir J 36:143–150PubMedCrossRefGoogle Scholar
  2. Del Rio R, Moya EA, Iturriaga R (2011) Differential expression of pro-inflammatory cytokines, endothelin-1 and nitric oxide synthases in the rat carotid body exposed to intermittent hypoxia. Brain Res 1395:74–85PubMedCrossRefGoogle Scholar
  3. Del Rio R, Moya EA, Parga MJ, Madrid C, Iturriaga R (2012) Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia. Eur Respir J 39:1492–1500PubMedCrossRefGoogle Scholar
  4. Del Rio R, Marcus NJ, Schultz HD (2013) Carotid chemoreceptor ablation improves survival in heart failure: rescuing autonomic control of cardiorespiratory function. J Am Coll Cardiol 62:2422–2430PubMedCrossRefGoogle Scholar
  5. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47–112PubMedCrossRefPubMedCentralGoogle Scholar
  6. Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33:1195–1205PubMedCrossRefGoogle Scholar
  7. Greenberg HE, Sica A, Batson D, Scharf SM (1999) Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia. J Appl Physiol 86:298–305PubMedGoogle Scholar
  8. Iturriaga R, Moya EA, Del Rio R (2009) Carotid body potentiation induced by intermittent hypoxia: implications for cardiorespiratory changes induced by sleep apnoea. Clin Exp Pharmacol Physiol 36:1197–1204PubMedCrossRefGoogle Scholar
  9. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB (2006) Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats. J Appl Physiol 100:1974–1982PubMedCrossRefGoogle Scholar
  10. Mcbryde FD, Abdala AP, Hendy EB, Pijacka W, Marvar P, Moraes DJA, Sobotka PA, Paton JFR (2013) The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension. Nat Commun 4:2395PubMedCrossRefGoogle Scholar
  11. Paton JFR, Sobotka PA, Fudim M, Engelman ZJ, Hart ECJ, Mcbryde FD, Abdala AP, Marina N, Gourine AV, Lobo M, Patel N, Burchell A, Ratcliffe L, Nightingale A (2013) The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases. Hypertension 61:5–13PubMedCrossRefGoogle Scholar
  12. Pawar A, Nanduri J, Yuan G, Khan SA, Wang N, Kumar GK, Prabhakar NR (2009) Reactive oxygen species-dependent endothelin signaling is required for augmented hypoxic sensory response of the neonatal carotid body by intermittent hypoxia. Am J Physiol Regul Integr Comp Physiol 296:R735–R742PubMedCrossRefPubMedCentralGoogle Scholar
  13. Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci U S A 100:10073–10078PubMedCrossRefPubMedCentralGoogle Scholar
  14. Prabhakar NR, Peng YJ, Jacono FJ, Kumar GK, Dick TE (2005) Cardiovascular alterations by chronic intermittent hypoxia: importance of carotid body chemoreflexes. Clin Exp Pharmacol Physiol 32:447–449PubMedCrossRefGoogle Scholar
  15. Rey S, Del Rio R, Alcayaga J, Iturriaga R (2004) Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia. J Physiol 560:577–586PubMedCrossRefPubMedCentralGoogle Scholar
  16. Rey S, Tarvainen MP, Karjalainen PA, Iturriaga R (2008) Dynamic time-varying analysis of heart rate and blood pressure variability in cats exposed to short-term chronic intermittent hypoxia. Am J Physiol Regul Integr Comp Physiol 295:R28–R37PubMedCrossRefGoogle Scholar
  17. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) Sleep apnea and cardiovascular disease. J Am Coll Cardiol 52:686–717PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rodrigo Iturriaga
    • 1
    Email author
  • David C. Andrade
    • 1
  • Rodrigo Del Rio
    • 2
  1. 1.Laboratorio de Neurobiología, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Laboratorio de Control Cardiorrespiratorio. Centro de Investigación BiomédicaUniversidad Autónoma de ChileSantiagoChile

Personalised recommendations