Abstract
During hypoxic or hypoxemic conditions, tissue oxygenation and arterial O2 carrying capacity are upregulated by two complementary systems, namely the neural respiratory network (central and peripheral) that leads to increased minute ventilation thereby increasing tissue oxygenation, and erythropoietin (Epo) release by the kidney that activates erythropoiesis in bone marrow to augment arterial blood O2 carrying capacity. Despite the fact that both neural respiratory control and Epo-mediated elevation of red blood cells are responsible for keeping arterial O2 content optimal, no interaction between these systems has been described so far. Here we review data obtained in our laboratory demonstrating that ventilatory and erythropoietic systems are tightly connected. We found Epo is the key factor mediating this relationship through modulation of the chemoreflex pathway. Moreover, we showed that this interaction occurs in a sex-dependent manner.
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References
Banks WA, Jumbe NL, Farrell CL, Niehoff ML, Heatherington AC (2004) Passage of erythropoietic agents across the blood–brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa. Eur J Pharmacol 505:93–101
Behan M, Wenninger JM (2008) Sex steroidal hormones and respiratory control. Respir Physiol Neurobiol 164:213–221
Gassmann M, Soliz J (2009) Erythropoietin modulates the neural control of hypoxic ventilation. Cell Mol Life Sci 22:3575–3582
Hilaire G, Viemari JC, Coulon P, Simonneau M, Bévengut M (2004) Modulation of the respiratory rhythm generator by the pontine noradrenergic A5 and A6 groups in rodents. Respir Physiol Neurobiol 143(2–3):187–197
Jelkmann W (2007) Erythropoietin after a century of research: younger than ever. Eur J Haematol 78:183–205
Kellert BA, McPherson RJ, Juul SE (2007) A comparison of high-dose recombinant erythropoietin treatment regimens in brain-injured neonatal rats. Pediatr Res 61:451–455
Kemp PJ (2006) Detecting acute changes in oxygen: will the real sensor please stand up? Exp Physiol 91:829–834
Kumral A, Baskin H, Yesilirmak DC, Ergur BU, Aykan S, Genc S, Genc K, Yilmaz O, Tugyan K, Giray O, Duman N, Ozkan H (2007) Erythropoietin attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain. Neonatology 92:269–278
Kumral A, Tuzun F, Oner MG, Genc S, Duman N, Ozkan H. (2011). Erythropoietin in neonatal brain protection: The past, the present and the future. Brain Dev. 8:632–43
Lam SY, Tipoe GL, Fung ML (2009) Upregulation of erythropoietin and its receptor expression in the rat carotid body during chronic and intermittent hypoxia. Adv Exp Med Biol 648:207–214
Lopez-Barneo J, Ortega-Saenz P, Pardal R, Pascual A, Piruat JI (2008) Carotid body oxygen sensing. Eur Respir J 32:1386–1398
Ortega-Saenz P, Pascual A, Piruat JI, Lopez-Barneo J (2007) Mechanisms of acute oxygen sensing by the carotid body: lessons from genetically modified animals. Respir Physiol Neurobiol 157:140–147
Rabie T, Marti HH (2008) Brain protection by erythropoietin: a manifold task. Physiology (Bethesda) 23:263–274
Ruschitzka FT, Wenger RH, Stallmach T, Quaschning T, de Wit C, Wagner K, Labugger R, Kelm M, Noll G, Rülicke T, Lindberg RL, Rodenwaldt B, Bauer C, Lüscher TF, Gassmann M (2000) Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proc Natl Acad Sci U S A 97:11609–11613
Sasaki R, Masuda S, Sasaki R, Masuda S, Nagao M (2001) Pleiotropic functions and tissue-specific expression of erythropoietin. News Physiol Sci 16:110–113
Soliz J, Joseph V (2005) Perinatal steroid exposure and respiratory control during early postnatal life. Respir Physiol Neurobiol 149(1–3):111–122
Soliz J, Joseph V, Soulage C, Becskei C, Vogel J, Pequignot JM, Ogunshola O, Gassmann M (2005) Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies. J Physiol 568:559–571
Soliz J, Thomsen JJ, Soulage C, Lundby C, Gassmann M (2009) Sex-dependent regulation of hypoxic ventilation in mice and humans is mediated by erythropoietin. Am J Physiol Regul Integr Comp Physiol 296:R1837–R1846
Tempera A, Stival E, Piastra M, DEL D, Ottaviano C, Tramontozzi P, Marconi M, Cafforio C, Marcozzi P, Rossi N, Buffone E (2011) Early erythropoietin influences both transfusion and ventilation need in very low birth weight infants. J Matern Fetal Neonatal Med 24:1060–1064
Xenocostas A, Cheung WK, Farrell F, Zakszewski C, Kelley M, Lutynski A, Crump M, Lipton JH, Kiss TL, Lau CY, Messner HA (2005) The pharmacokinetics of erythropoietin in the cerebrospinal fluid after intravenous administration of recombinant human erythropoietin. Eur J Clin Pharmacol 61:189–195
Acknowledgements
JS is supported by the Respiratory Health Network of the FRSQ (Fonds de la Recherche en Santé du Québec), the Foundation of Stars for the Children’s health research, the CHUQ Research Center direction and axis on Reproduction, perinatal health, and child health, and Faculty of Medicine of Laval University. We apologize to the many researchers who contributed importantly to the field of research and whose works were not cited due to space restriction.
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Soliz, J., Khemiri, H., Caravagna, C., Seaborn, T. (2012). Erythropoietin and the Sex-Dimorphic Chemoreflex Pathway. In: Nurse, C., Gonzalez, C., Peers, C., Prabhakar, N. (eds) Arterial Chemoreception. Advances in Experimental Medicine and Biology, vol 758. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4584-1_8
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DOI: https://doi.org/10.1007/978-94-007-4584-1_8
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