Sex-specific effects of chronic hypoxia on routine cardiovascular function and metabolism in CD-1 mice

Hypoxia can have significant impacts on cardiovascular physiology, but the effects of chronic exposure to moderate hypoxia and how they differ between sexes remain poorly understood. We used physiological telemetry to examine this issue in CD-1 mice. Adult mice were chronically exposed to normoxia or hypobaric hypoxia (12 kPa O₂) for 6 wk and then subjected to telemetry measurements of routine physiology across the diel cycle. Heart rate (f_H), mean arterial blood pressure (P_mean), body temperature (T_b), and activity were greater during the nighttime active phase than the daytime inactive phase. Chronic hypoxia had no effect on these traits at night but had sex-specific effects during the day, when chronic hypoxia reduced f_H, T_b, and activity in males but not females. These differences existed without any effect of chronic hypoxia on α-adrenergic or nitric oxide tone on the vasculature (assessed as P_mean response to pharmacological blockade). Responses to acute hypoxia were then measured during stepwise reductions in inspired O₂ from 21 to 8 kPa O₂. O₂ consumption rate, f_H, P_mean, and T_b declined in severe hypoxia, but the O₂ tension at which this began was lower in mice held in chronic hypoxia. However, the hypoxic ventilatory response was augmented by exposure to chronic hypoxia in females but not in males. Females also exhibited larger increases in lung mass and less right ventricle hypertrophy than males in chronic hypoxia. Our results support the growing evidence that there can be considerable sex differences in the cardiorespiratory responses to hypoxia.