| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received June 23, 2005
Revised July 21, 2005
Accepted after revision July 21, 2005
1 Institute of Veterinary Physiology, University of Zurich
2 Centre de recherche CHUQ, Hôpital St Francois d'Assise
3 UMR CNRS 5123 - Physiologie Intégrative Cellulaire et Moléculaire
* To whom correspondence should be addressed. E-mail: maxg{at}access.unizh.ch.
Apart from its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions in brain, retina and heart upon ischemic injury. However, 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 apnea. These results imply that Epo in brain modulates ventilation. Additional analysis revealed that Epo receptor (EpoR) is expressed in the main brainstem respiratory centers 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 central (brainstem) and peripheral (carotid body) levels. The physiological relevance of these novel findings are useful to better understand respiratory disorders including those occurring at high altitude.
This article has been cited by other articles:
|
|
 |
|
  C. Lundby, P. Robach, R. Boushel, J. J. Thomsen, P. Rasmussen, M. Koskolou, and J. A. L. Calbet Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport? J Appl Physiol, August 1, 2008; 105(2): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Soliz, C. Soulage, E. Borter, M. T. van Patot, and M. Gassmann Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R649 - R658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Bavis, F. L. Powell, A. Bradford, C. C.W. Hsia, J. E. Peltonen, J. Soliz, B. Zeis, E. K. Fergusson, Z. Fu, M. Gassmann, et al. Respiratory plasticity in response to changes in oxygen supply and demand Integr. Comp. Biol., October 1, 2007; 47(4): 532 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Soliz, C. Soulage, D. M. Hermann, and M. Gassmann Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1702 - R1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Soliz, M. Gassmann, and V. Joseph Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia J. Physiol., August 15, 2007; 583(1): 329 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Schaffer, J. Vogel, C. Breymann, M. Gassmann, and H. H. Marti Preserved placental oxygenation and development during severe systemic hypoxia Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R844 - R851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. O. Ogunshola, V. Djonov, R. Staudt, J. Vogel, and M. Gassmann Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R678 - R684. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
