Top

Published in:

01-01-2021 | Original Article

Adaptative mechanism of the equilibrative nucleoside transporter 1 (ENT-1) and blood adenosine levels in elite freedivers

Authors: M. Marlinge, D. Vairo, A. Bertaud, C. Vernet, M. Chefrour, L. Bruzzese, M. C. Chaptal, G. Mottola, A. Boussuges, J. J. Risso, M. Blot-Chabaud, M. Coulange, R. Guieu, F. Joulia

Published in: European Journal of Applied Physiology | Issue 1/2021

Abstract

Purpose

Long static or intense dynamic apnoea-like high-altitude exposure is inducing hypoxia. Adenosine is known to participate to the adaptive response to hypoxia leading to the control of heart rate, blood pressure and vasodilation. Extracellular adenosine level is controlled through the equilibrative nucleoside transporter 1 (ENT-1) and the enzyme adenosine deaminase (ADA). The aim of this study was to determine the control of adenosine blood level (ABL) via ENT-1 and ADA during apnoea-induced hypoxia in elite freedivers was similar to high-altitude adaptation.

Methods

Ten freediver champions and ten controls were studied. Biological (e.g. ENT-1, ADA, ABL, PaO₂, PaCO₂ and pH) and cardiovascular (e.g. heart rate, arterial pressure) parameters were measured at rest and after a submaximal dry static apnoea.

Results

In freedivers, ABL was higher than in control participants in basal condition and increased more in response to apnoea. Also, freedivers showed an ADA increased in response to apnoea. Finally, ENT-1 level and function were reduced for the free divers.

Conclusion

Our results suggest in freedivers the presence of an adaptive mechanism similar to the one observed in human exposed to chronic hypoxia induced by high-altitude environment.

Andersson J, Schagatay E (1998) Arterial oxygen desaturation during apnea in humans. Undersea Hyperb Med 25:21–25PubMed

Attias J, Bieles J, Carvil P, Laing C, Lewis F, Jaka O, O’Brien K, Ruchaya P (2017) Altitude exposure and increased heart rate: the role of the parasympathetic nervous system. J Physiol (Lond) 595:4589–4590

Bain AR, Drvis I, Dujic Z, MacLeod DB, Ainslie PN (2018) Physiology of static breath holding in elite apneists. Exp Physiol 103:635–651PubMed

Baldwin SA, Beal PR, Yao SYM, King AE, Cass CE, Young JD (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447:735–743PubMed

Bärtsch P, Gibbs JSR (2007) Effect of altitude on the heart and the lungs. Circulation 116:2191–2202PubMed

Bonello L, Laine M, Kipson N, Mancini J, Helal O, Fromonot J, Gariboldi V, Condo J, Thuny F, Frere C, Camoin-Jau L, Paganelli F, Dignat-George F, Guieu R (2014) Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome. J Am Coll Cardiol 63:872–877PubMed

Boussuges A, Gavarry O, Bessereau J, Coulange M, Bourc’his M, Rossi P (2014) Glossopharyngeal insufflation and breath-hold diving: the more, the worse? Wilderness Environ Med 25:466–471PubMed

Bruzzese L, Fromonot J, By Y, Durand-Gorde J-M, Condo J, Kipson N, Guieu R, Fenouillet E, Ruf J (2014) NF-κB enhances hypoxia-driven T-cell immunosuppression via upregulation of adenosine A(2A) receptors. Cell Signal 26:1060–1067PubMed

Bruzzese L, Rostain J-C, Née L, Condo J, Mottola G, Adjriou N, Mercier L, Berge-Lefranc J-L, Fromonot J, Kipson N, Lucciano M, Durand-Gorde J-M, Jammes Y, Guieu R, Ruf J, Fenouillet E (2015) Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat. J Appl Physiol 119:140–147PubMed

Bulmer AC, Coombes JS, Sharman JE, Stewart IB (2008) Effects of maximal static apnea on antioxidant defenses in trained free divers. Med Sci Sports Exerc 40:1307–1313PubMed

Casanello P, Torres A, Sanhueza F, González M, Farías M, Gallardo V, Pastor-Anglada M, San Martín R, Sobrevia L (2005) Equilibrative nucleoside transporter 1 expression is downregulated by hypoxia in human umbilical vein endothelium. Circ Res 97:16–24PubMed

Coney AM, Marshall JM (1998) Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia. J Physiol (Lond) 509(Pt 2):507–518

Eichhorn L, Erdfelder F, Kessler F, Dolscheid-Pommerich RC, Zur B, Hoffmann U, Ellerkmann RE, Meyer R (2017) Influence of apnea-induced hypoxia on catecholamine release and cardiovascular dynamics. Int J Sports Med 38:85–91PubMed

Eltzschig HK, Abdulla P, Hoffman E, Hamilton KE, Daniels D, Schönfeld C, Löffler M, Reyes G, Duszenko M, Karhausen J, Robinson A, Westerman KA, Coe IR, Colgan SP (2005) HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J Exp Med 202:1493–1505PubMedPubMedCentral

Eltzschig HK, Faigle M, Knapp S, Karhausen J, Ibla J, Rosenberger P, Odegard KC, Laussen PC, Thompson LF, Colgan SP (2006) Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood 108:1602–1610PubMedPubMedCentral

Fagoni N, Sivieri A, Antonutto G, Moia C, Taboni A, Bringard A, Ferretti G (2015) Cardiovascular responses to dry resting apnoeas in elite divers while breathing pure oxygen. Respir Physiol Neurobiol 219:1–8PubMed

Feoktistov I, Ryzhov S, Zhong H, Goldstein AE, Matafonov A, Zeng D, Biaggioni I (2004) Hypoxia modulates adenosine receptors in human endothelial and smooth muscle cells toward an A2B angiogenic phenotype. Hypertension 44:649–654PubMed

Ferretti G, Costa M (2003) Diversity in and adaptation to breath-hold diving in humans. Comp Biochem Physiol Part A Mol Integr Physiol 136:205–213

Görlach A (2005) Control of adenosine transport by hypoxia. Circ Res 97:1–3PubMed

Iwamoto T, Umemura S, Toya Y, Uchibori T, Kogi K, Takagi N, Ishii M (1994) Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells. Biochem Biophys Res Commun 199:905–910PubMed

Joulia F, Steinberg JG, Faucher M, Jamin T, Ulmer C, Kipson N, Jammes Y (2003) Breath-hold training of humans reduces oxidative stress and blood acidosis after static and dynamic apnea. Respir Physiol Neurobiol 137:19–27PubMed

Joulia F, Coulange M, Lemaitre F, Costalat G, Franceschi F, Gariboldi V, Nee L, Fromonot J, Bruzzese L, Gravier G, Kipson N, Jammes Y, Boussuges A, Brignole M, Deharo JC, Guieu R (2013) Plasma adenosine release is associated with bradycardia and transient loss of consciousness during experimental breath-hold diving. Int J Cardiol 168:e138–e141PubMed

Joulia F, Coulange M, Desplantes A, Barberon B, Kipson N, Gerolami V, Jammes Y, Kerbaul F, Née L, Fromonot J, Bruzzese L, Michelet P, Boussuges A, Brignole M, Deharo J-C, Guieu R (2014) Purinergic profile of fainting divers is different from patients with vasovagal syncope. Int J Cardiol 174:741–743PubMed

Keil VC, Eichhorn L, Mutsaerts HJMM, Träber F, Block W, Mädler B, van de Ven K, Siero JCW, MacIntosh BJ, Petr J, Fimmers R, Schild HH, Hattingen E (2018) Cerebrovascular reactivity during prolonged breath-hold in experienced freedivers. AJNR Am J Neuroradiol 39:1839–1847PubMedPubMedCentral

Liu H et al (2016) Beneficial role of erythrocyte adenosine A2B receptor-mediated AMPK activation in high altitude hypoxia. Circulation 134:405–421PubMedPubMedCentral

Maille B et al (2019) Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion. Purinergic Signal 15:45PubMed

Marlinge M, Vairo D, Marolda V, Bruzzese L, Adjriou N, Guiol C, Kipson N, Bonardel A, Gastaldi M, Kerbaul F, Michelet P, Deharo JC, Mottola G, Mace P, Chefrour M, Guieu R (2017) Rapid measurement of adenosine concentration in human blood using fixed potential amperometry: comparison with mass spectrometry and high-performance liquid chromatography. J Anal Bioanal Technol 8:4

Moore LG (2017) Measuring high-altitude adaptation. J Appl Physiol 123:1371–1385PubMedPubMedCentral

Morelli MS, Greco A, Valenza G, Giannoni A, Emdin M, Scilingo EP, Vanello N (2018) Analysis of generic coupling between EEG activity and PETCO₂ in free breathing and breath-hold tasks using maximal information coefficient (MIC). Sci Rep 8:4492PubMedPubMedCentral

Morote-Garcia JC, Rosenberger P, Kuhlicke J, Eltzschig HK (2008) HIF-1-dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak. Blood 111:5571–5580PubMed

Paganelli F, Resseguier N, Marlinge M, Laine M, Malergue F, Kipson N, Armangau P, Pezzoli N, Kerbaul F, Bonello L, Mottola G, Fenouillet E, Guieu R, Ruf J (2018) Specific pharmacological profile of A2A adenosine receptor predicts reduced fractional flow reserve in patients with suspected coronary artery disease. J Am Heart Assoc 7:e008290PubMedPubMedCentral

Plagemann PGW (1986) Transport and metabolism of adenosine in human erthrocytes: effect of transport inhibitors and regulation by phosphate. J Cell Physiol 128:491–500PubMed

Ruf J, Paganelli F, Bonello L, Kipson N, Mottola G, Fromonot J, Condo J, Boussuges A, Bruzzese L, Kerbaul F, Jammes Y, Gariboldi V, Franceschi F, Fenouillet E, Guieu R (2016) Spare adenosine A2a receptors are associated with positive exercise stress test in coronary artery disease. Mol Med 22:530–536PubMedPubMedCentral

Ruf J, Vairo D, Paganelli F, Guieu R (2019) Extracellular vesicles with ubiquitinated adenosine A2A receptor in plasma of patients with coronary artery disease. J Cell Mol Med 23:6805–6811PubMedPubMedCentral

Sacramento JF, Melo BF, Conde SV (2018) Adenosine mediates hypercapnic response in the rat carotid body via A2A and A2B receptors. Adv Exp Med Biol 1071:89–93PubMed

Sampol J, Dussol B, Fenouillet E, Capo C, Mege JL, Halimi G, Bechis G, Brunet P, Rochat H, Berland Y, Guieu R (2001) High adenosine and deoxyadenosine concentrations in mononuclear cells of hemodialyzed patients. J Am Soc Nephrol 12:1721–1728PubMed

Shah N, Bye K, Marshall A, Woods DR, O’Hara J, Barlow M, Rimmer J, Boos CJ (2020) The effects of apnea training, using voluntary breath holds, on high altitude acclimation: breathe-high altitude study. High Alt Med Biol 21:152–159PubMed

Song A et al (2017) Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent. Nat Commun 8:14108PubMedPubMedCentral

Taboni A, Vinetti G, Bruseghini P, Camelio S, D’Elia M, Moia C, Ferretti G, Fagoni N (2018) Cardiovascular responses to dry apnoeas at exercise in air and in pure oxygen. Respir Physiol Neurobiol 255:17–21PubMed

Taboni A, Fagoni N, Moia C, Vinetti G, Ferretti G (2019) Gas exchange and cardiovascular responses during breath-holding in divers. Respir Physiol Neurobiol 267:27–34PubMed

Vinetti G, Lopomo NF, Taboni A, Fagoni N, Ferretti G (2020) The current use of wearable sensors to enhance safety and performance in breath-hold diving: a systematic review. Diving Hyperb Med 50:54–65PubMed

Title: Adaptative mechanism of the equilibrative nucleoside transporter 1 (ENT-1) and blood adenosine levels in elite freedivers
Authors: M. Marlinge
D. Vairo
A. Bertaud
C. Vernet
M. Chefrour
L. Bruzzese
M. C. Chaptal
G. Mottola
A. Boussuges
J. J. Risso
M. Blot-Chabaud
M. Coulange
R. Guieu
F. Joulia
Publication date: 01-01-2021
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Applied Physiology / Issue 1/2021
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-020-04523-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Adaptative mechanism of the equilibrative nucleoside transporter 1 (ENT-1) and blood adenosine levels in elite freedivers

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure

Effects of trunk lean and foot lift exercises in sitting position on abdominal muscle activity and the contribution rate of transversus abdominis

Effects of a lower limb muscular fatigue on posture–movement interaction during a lower limb pointing task

A flow resistive inspiratory muscle training mask worn during high-intensity interval training does not improve 5 km running time-trial performance

Low energy availability: history, definition and evidence of its endocrine, metabolic and physiological effects in prospective studies in females and males

Effects of acute and sub-acute hypobaric hypoxia on oxidative stress: a field study in the Alps