Adenosine Receptor Blockade by Caffeine Inhibits Carotid Sinus Nerve Chemosensory Activity in Chronic Intermittent Hypoxic Animals
- 8 Citations
- 1 Mentions
- 2.2k Downloads
Abstract
Adenosine is a key excitatory neurotransmitter at the synapse between O2-sensing chemoreceptor cells-carotid sinus nerve (CSN) endings in the carotid body (CB). Herein, we have investigated the significance of adenosine, through the blockade of its receptors with caffeine, on the CB hypoxic sensitization induced by chronic intermittent hypoxia (CIH) in the rat. CIH animals were obtained by submitting rats during 15 days from 8:00 to 16:00 to 10 %O2 for 40 s and 20 % O2 for 80 s (i.e., 30 episodes/h). Caffeine (1 mM) was tested in spontaneous and 5 %O2 evoked-CSN chemosensory activity in normoxic and CIH animals. CIH decreased basal spontaneous activity but increased significantly CSN activity evoked by acute hypoxia. Caffeine did not modify basal spontaneous activity in normoxic rats, but decreased significantly by 47.83 % basal activity in CIH animals. In addition, acute application of caffeine decreased 49.31 % and 56.01 % the acute hypoxic response in normoxic and CIH animals, respectively. We demonstrate that adenosine contributes to fix CSN basal activity during CIH, being also involved in hypoxic CB chemotransduction. It is concluded that adenosine participates in CB sensitization during CIH.
Keywords
Chronic intermittent hypoxia Hypoxic sensitization Adenosine Carotid sinus nerve activity CaffeineNotes
Acknowledgements
The work was supported by FCT Grant (Ref: EXPL/NEU-SCC/2183/2013) from Portugal and by the Spanish Grants BFU2012-37459 and CIBERES to C.G.
References
- Conde SV, Monteiro EC (2004) Hypoxia induces adenosine release from the rat carotid body. J Neurochem 89:1148–1156PubMedCrossRefGoogle Scholar
- Conde SV, Obeso A, Vicario I, Rigual R, Rocher A, Gonzalez C (2006) Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors. J Neurochem 98:616–628PubMedCrossRefGoogle Scholar
- Conde SV, Monteiro EC, Obeso A, Gonzalez C (2009) Adenosine in peripheral chemoreception: new insights into a historically overlooked molecule. Adv Exp Med Biol 648:159–174Google Scholar
- Conde SV, Monteiro EC, Rigual R, Obeso A, Gonzalez C (2012a) Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity. J Appl Physiol 112:2002–2010PubMedCrossRefGoogle Scholar
- Conde SV, Ribeiro MJ, Obeso A, Rigual R, Monteiro EC, Gonzalez C (2012b) Chronic caffeine intake in adult rat inhibits carotid body sensitization produced by chronic sustained hypoxia but maintains intact chemoreflex output. Mol Pharmacol 82:1056–1065PubMedCrossRefGoogle Scholar
- Fredholm BB, Battig K, Holemn J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133PubMedGoogle Scholar
- Gonzalez-Martín MC, Vega-Agapito MV, Conde SV, Castañeda J, Bustamante R, Olea E, Perez-Vizcaino F, Gonzalez C, Obeso A (2011) Carotid body function and ventilatory responses in intermittent hypoxia. Evidence for anomalous brainstem integration of arterial chemoreceptor input. J Cell Physiol 226:1961–1969PubMedCrossRefGoogle Scholar
- Lavie L (2003) Obstructive sleep apnoea syndrome – an oxidative stress disorder. Sleep Med Rev 7:35–51PubMedCrossRefGoogle Scholar
- Narkiewicz K, van de Borne PJ, Pesek CA, Dyken ME, Montano N, Somers VK (1999) Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea. Circulation 99:1183–1189PubMedCrossRefGoogle Scholar
- Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory longterm facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci U S A 100:10073–10078PubMedCrossRefPubMedCentralGoogle Scholar
- Prabhakar NR, Dick TE, Nanduri J, Kumar GK (2007) Systemic, cellular and molecular analysis of chemoreflex-mediated sympathoexcitation by chronic intermittent hypoxia. Exp Physiol 92:39–44PubMedCrossRefGoogle Scholar
- 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
- Rigual R, Rico AJ, Prieto-Lloret J, de Felipe C, Gonzalez C, Donnelly DF (2002) Chemoreceptor activity is normal in mice lacking the NK1 receptor. Eur J Neurosci 16:2078–2084PubMedCrossRefGoogle Scholar
- Somers VK, Dyken ME, Clary MP, Abboud FM (1995) Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96:1897–1904PubMedCrossRefPubMedCentralGoogle Scholar