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

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

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

Jorge Soliz,Christophe Soulage,Dirk M Hermann,Max Gassmann,

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 approximately 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.

Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin. Publishing Authors By Initials

J Soliz,C Soulage,DM Hermann,M Gassmann,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Regulatory, integr

VOLUME: 293

Page Numbers: R1702-10

Journal Abbreviation: Am. J. Physiol. Regul. Integr.

ISSN: 0363-6119

DAY: 25

MONTH: 07

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 100901230

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Grant and Affiliation Information for Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin.

AFFILIATION: Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.

Country: United States

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MEDLINETA: Am J Physiol Regul Integr Comp

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