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

Elliot-Portal, Elizabeth; Schneider-Gasser, Edith-M.; Revollo, Susana; Soliz, Jorge; Voituron, Nicolas; Laouafa, Sofien; Gassmann, Max; Joseph, Vincent

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.ispartofseries	American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
dc.rights	info:eu-repo/semantics/restrictedAccess
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#3.01.08
dc.relation.issn	1522-1490