We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), display divergent physiological responses to high altitude, including improved respiratory and metabolic control in mice. In the present study, we asked whether these traits would also be present in response to hypoxia at sea level. To answer this question, we exposed rats (Sprague Dawley) and mice (FVB) to normoxia (21% O2) or hypoxia (15 and 12% O2) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1α (ELISA and mass spectrometry) and other proteins whose expression are regulated by hypoxia (glucose transporter 1, pyruvate dehydrogenase kinase 1 and angiopoietin 2; mass spectrometry) in the brainstem. In response to hypoxia, compared with rats, mice had higher minute ventilation, lower metabolic rate and higher expression of HIF-1α in the brainstem. In mice, the expression level of HIF-1α was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O2, while expression of the glucose transporter 1 increased. We conclude that mice and rats raised at sea level have divergent physiological and molecular responses to hypoxia, supporting the hypothesis that mice have innate traits that favor adaptation to altitude.
The authors declare no competing or financial interests.
V.J., J.S. and A.J.-L. developed the concepts and designed the experiments. A.J.-L., M.S. and V.J. performed the experiments. A.J.-L., M.S. and V.J. analyzed the data and prepared the figures. V.J., J.S. and A.J.-L. prepared or edited the manuscript prior to submission.
This study was funded by the Natural Sciences and Engineering Research Council of Canada (grant RGPGP-2014-00083). A.J.-L. was supported by a training grant in respiratory physiology from Réseau en Santé Réspiratoire (Fonds de Recherche du Québec – Santé, and the Canadian Institutes of Health Research).
- Received May 11, 2016.
- Accepted October 6, 2016.
- © 2016. Published by The Company of Biologists Ltd