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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/R1702    most recent 00350.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Soliz, J. Articles by Gassmann, M. Search for Related Content PubMed PubMed Citation Articles by Soliz, J. Articles by Gassmann, M.

ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin

¹Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich; ²Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, Université Claude Bernard, Villeurbanne Cedex, France; ³Department of Neurology, University Hospital Zurich, Zurich, Switzerland

Submitted 18 May 2007 ; accepted in final form 19 July 2007

Apart from enhancing red blood cell production, erythropoietin (Epo) has been shown to modulate the ventilatory response to reduced oxygen supply. Both functions are crucial for the organism to cope with increased oxygen demand. In the present work, we analyzed the impact of Epo and the resulting excessive erythrocytosis in the neural control of normoxic and hypoxic ventilation. To this end, we used our transgenic mouse line (Tg6) that shows high levels of human Epo in brain and plasma, the latter leading to a hematocrit of 80%. Interestingly, while normoxic and hypoxic ventilation in Tg6 mice was similar to WT mice, Tg6 mice showed an increased respiratory frequency but a decreased tidal volume. Knowing that Epo modulates catecholaminergic activity, the altered catecholaminergic metabolism measured in brain stem suggested that the increased respiratory frequency in Tg6 mice was related to the overexpression of Epo in brain. In the periphery, higher response to hyperoxia (Dejours test), as well as reduced tyrosine hydroxylase activity in carotid bodies, revealed a higher chemosensitivity to oxygen in transgenic mice. Moreover, in line with the decreased activity of the rate-limiting enzyme for dopamine synthesis, the intraperitoneal injection of a highly specific peripheral ventilatory stimulant, domperidone, did not stimulate hypoxic ventilatory response in Tg6 mice. These results suggest that high Epo plasma levels modulate the carotid body's chemotransduction. All together, these findings are relevant for understanding the cross-talk between the ventilatory and erythropoietic systems exposed to hypoxia.

carotid body; brain stem; ventilatory control

This article has been cited by other articles:

				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]