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Gender‐dependent regulation of hypoxic ventilation in mouse and man is mediated by erythropoietin
Author(s) -
Gassmann Max,
Soliz Jorge
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1173.17
Subject(s) - erythropoietin , hypoxic ventilatory response , hypoxia (environmental) , endocrinology , hyperoxia , medicine , erythropoiesis , ventilation (architecture) , hypercapnia , peripheral chemoreceptors , hypoxic hypoxia , hormone , respiratory system , biology , carotid body , oxygen , lung , chemistry , anemia , electrophysiology , mechanical engineering , organic chemistry , engineering
Acclimatization to hypoxic exposure relies on an elevated ventilation and erythropoietic activity. We recently showed that erythropoietin (Epo) links both responses: apart from its well‐known function on erythropoiesis, cerebral and plasma Epo interferes with the central respiratory centers (brainstem) and peripheral chemoreceptors (carotid bodies). Knowing that women cope better than men to reduced oxygen supply (as observed at high altitude), we analyzed the hypoxic ventilatory response in female mice. We used either transgenic mice with elevated Epo levels in brain only (Tg21), or in brain and plasma (Tg6) or wt animals injected or not with rhEpo. Exposure of these animals to moderate and severe acute hypoxia as well as to hyperoxia and injection of domperidone, reveled that the presence of Epo extensively increases the hypoxic ventilatory response in female mice compared to their male siblings. Furthermore, we showed that soluble EpoR (sEpoR) is endogenously synthesized by neural tissue, and abolishes the ventilatory acclimatization to hypoxia when infused in brain. Finally, human volunteers were injected rhEpo and subsequently exposed to 10% oxygen. Compared to men, the hypoxic ventilatory response was significantly increased in women. We conclude that Epo exerts a gender‐dependent effect on hypoxic ventilation most probably involving sexual hormones.