HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/R1837    most recent 90967.2008v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Google Scholar Articles by Soliz, J. Articles by Gassmann, M. PubMed PubMed Citation Articles by Soliz, J. Articles by Gassmann, M.

EXERCISE AND RESPIRATORY PHYSIOLOGY

Sex-dependent regulation of hypoxic ventilation in mice and humans is mediated by erythropoietin

¹Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; ²Copenhagen Muscle Research Centre, Copenhagen, Denmark; ³Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, Villeurbanne Cedex, France; and ⁴Department of Sport Science, University of Århus, Denmark

Submitted 28 November 2008 ; accepted in final form 20 March 2009

Acclimatization to hypoxic exposure relies on an elevated ventilation and erythropoietic activity. We recently proposed that erythropoietin (Epo) links both responses: apart from red blood cell production, cerebral and plasma Epo interact with the central and peripheral respiratory centers. Knowing that women cope better than men with reduced oxygen supply (as observed at high altitude), we analyzed the hypoxic ventilatory response in Epo-overexpressing transgenic male and female mice with high Epo levels in brain and plasma (Tg6) or in wild-type animals injected with recombinant human Epo (rhEpo). Exposure to moderate and severe hypoxia as well as to hyperoxia and injection of domperidone, a potent peripheral ventilatory stimulant, revealed that the presence of transgenic or rhEpo extensively increased the hypoxic ventilatory response in female mice compared with their corresponding male siblings. Alterations of catecholamines in the brain stem's respiratory centers were also sex dependent. In a proof-of-concept study, human volunteers were intravenously injected with 5,000 units rhEpo and subsequently exposed to 10% oxygen. Compared with men, the hypoxic ventilatory response was significantly increased in women. We conclude that Epo exerts a sex-dependent impact on hypoxic ventilation improving the response in female mice and in women that most probably involves sexual hormones. Our data provides an explanation as to why women are less susceptible to hypoxia-associated syndromes than men.

carotid body; brain stem; sexual dimorphism