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Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies
Author(s) -
Soliz Jorge,
Joseph Vincent,
Soulage Christophe,
Becskei Csilla,
Vogel Johannes,
Pequignot Jean Marc,
Ogunshola Omolara,
Gassmann Max
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.093328
Subject(s) - erythropoietin , brainstem , ventilation (architecture) , hypoxic ventilatory response , carotid body , hypoxia (environmental) , control of respiration , medicine , erythropoietin receptor , endocrinology , respiratory system , peripheral chemoreceptors , biology , chemistry , electrophysiology , mechanical engineering , organic chemistry , oxygen , engineering
Apart from its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions in brain, retina and heart upon ischaemic injury. However, the physiological non‐erythroid functions of Epo remain unclear. Here we use a transgenic mouse line (Tg21) constitutively overexpressing human Epo in brain to investigate Epo's impact on ventilation upon hypoxic exposure. Tg21 mice showed improved ventilatory response to severe acute hypoxia and moreover improved ventilatory acclimatization to chronic hypoxic exposure. Furthermore, following bilateral transection of carotid sinus nerves that uncouples the brain from the carotid body, Tg21 mice adapted their ventilation to acute severe hypoxia while chemodenervated wild‐type (WT) animals developed a life‐threatening apnoea. These results imply that Epo in brain modulates ventilation. Additional analysis revealed that the Epo receptor (EpoR) is expressed in the main brainstem respiratory centres and suggested that Epo stimulates breathing control by alteration of catecholaminergic metabolism in brainstem. The modulation of hypoxic pattern of ventilation after i.v. injection of recombinant human Epo in WT mice and the dense EpoR immunosignal observed in carotid bodies showed that these chemoreceptors are sensitive to plasma levels of Epo. In summary, our results suggest that Epo controls ventilation at the central (brainstem) and peripheral (carotid body) levels. These novel findings are relevant to understanding better respiratory disorders including those occurring at high altitude.