Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis
| Autor: | Nicolas Voituron, Vincent Joseph, Edith M. Schneider Gasser, Jorge Soliz, Susana Revollo, Max Gassmann, Sofien Laouafa, Elizabeth Elliot-Portal |
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| Přispěvatelé: | University of Zurich, Soliz, Jorge |
| Rok vydání: | 2016 |
| Předmět: |
Male
Physiology CO2 chemosensitivity 030204 cardiovascular system & hematology Polycythemia/complications/physiopathology Hypercapnia Mice 2737 Physiology (medical) 0302 clinical medicine chronic mountain sickness purl.org/pe-repo/ocde/ford#3.01.08 [https] Brain 10081 Institute of Veterinary Physiology carotid body Mice transgenic Chronic mountain sickness medicine.anatomical_structure 10076 Center for Integrative Human Physiology Carotid body erythropoietin medicine.symptom medicine.drug Genetically modified mouse medicine.medical_specialty Mice Transgenic Polycythemia transgenic mice Carbon Dioxide/blood 03 medical and health sciences Carbon dioxide blood Physiology (medical) Internal medicine Respiration Erythropoietin/metabolism medicine Animals Brain/metabolism Erythropoietin business.industry hypercapnia 1314 Physiology Carbon Dioxide medicine.disease Hypercapnia/etiology/physiopathology Mice Inbred C57BL Endocrinology 570 Life sciences biology brain stem Pulmonary Ventilation business respiration 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Physiology |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.00226.2016 |
| Popis: | 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 (V̇) and CO production (V̇)], 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. |
| Databáze: | OpenAIRE |
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