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Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis

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dc.contributor.author Laouafa, Sofien
dc.contributor.author Elliot-Portal, Elizabeth
dc.contributor.author Revollo, Susana
dc.contributor.author Schneider-Gasser, Edith-M.
dc.contributor.author Joseph, Vincent
dc.contributor.author Voituron, Nicolas
dc.contributor.author Gassmann, Max
dc.contributor.author Soliz, Jorge
dc.date.accessioned 2019-02-06T14:45:36Z
dc.date.available 2019-02-06T14:45:36Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5097
dc.description.abstract The impact of cerebral erythropoietin (Epo) in the regulation of the hypercapnic ventilatory response (HcVR) is controversial. While we reported that cerebral Epo does not affect the central chemosensitivity in C57Bl6 mice receiving an intracisternal injection of sEpoR (the endogenous antagonist of Epo), a recent study in transgenic mice with constitutive high levels of human Epo in brain and circulation (Tg6) and in brain only (Tg21), showed that Epo blunts the HcVR, maybe by interacting with central and peripheral chemoreceptors. High Epo serum levels in Tg6 mice lead to excessive erythrocytosis (hematocrit ~80-90%), the main symptom of chronic mountain sickness (CMS). These latter results support the hypothesis that reduced central chemosensitivity accounts for the hypoventilation observed in CMS patients. To solve this intriguing divergence, we reevaluate HcVR in Tg6 and Tg21 mouse lines, by assessing the metabolic rate [O consumption (V) and CO production (V)], a key factor modulating ventilation, the effect of which was not considered in the previous study. Our results showed that the decreased HcVR observed in Tg6 mice (~70% reduction; < 0.01) was due to a significant decrease in the metabolism (~40%; < 0.0001) rather than Epo's effect on CO chemosensitivity. Additional analysis in Tg21 mice did not reveal differences of HcVR or metabolism. We concluded that cerebral Epo does not modulate the central chemosensitivity system, and that a metabolic effect upon CO inhalation is responsible for decreased HcVR observed in Tg6 animals. As CMS patients also show decreased HcVR, our findings might help to better understand respiratory disorders at high altitude. en_US
dc.language.iso eng
dc.publisher American Physiological Society
dc.relation.ispartof urn:issn:1522-1490
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject brain stem en_US
dc.subject carotid body en_US
dc.subject chronic mountain sickness en_US
dc.subject CO2 chemosensitivity en_US
dc.subject erythropoietin en_US
dc.subject hypercapnia en_US
dc.subject Pulmonary Ventilation en_US
dc.subject respiration en_US
dc.subject transgenic mice en_US
dc.subject Animals en_US
dc.subject Brain/metabolism en_US
dc.subject Carbon Dioxide/blood en_US
dc.subject Erythropoietin/metabolism en_US
dc.subject Hypercapnia/etiology/physiopathology en_US
dc.subject Male en_US
dc.subject Mice en_US
dc.subject Mice, Inbred C57BL en_US
dc.subject Mice, Transgenic en_US
dc.subject Polycythemia/complications/physiopathology en_US
dc.title Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1152/ajpregu.00226.2016
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE


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