Back to Search
Start Over
Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies.
- Source :
-
The Journal of physiology [J Physiol] 2005 Oct 15; Vol. 568 (Pt 2), pp. 559-71. Date of Electronic Publication: 2005 Jul 28. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Adaptation, Physiological
Animals
Atmosphere Exposure Chambers
Carotid Arteries innervation
Carotid Body drug effects
Denervation
Erythropoietin administration & dosage
Erythropoietin genetics
Erythropoietin pharmacology
Hypoxia metabolism
Immunohistochemistry
Mice
Mice, Transgenic
Norepinephrine metabolism
Oxygen Consumption
Receptors, Neurokinin-1 metabolism
Recombinant Proteins
Respiration
Respiratory Center drug effects
Tyrosine 3-Monooxygenase metabolism
Carotid Body metabolism
Erythropoietin physiology
Hypoxia physiopathology
Receptors, Erythropoietin metabolism
Respiratory Center metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3751
- Volume :
- 568
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- The Journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16051624
- Full Text :
- https://doi.org/10.1113/jphysiol.2005.093328