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

Abstract

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 weeks, and then subjected to telemetry measurements of routine physiology across the diel cycle. Heart rate (fH), mean arterial blood pressure (Pmean), body temperature (Tb), and activity were greater during the night-time active phase than the day-time inactive phase. Chronic hypoxia had no effect on these traits at night but had sex-specific effects during the day, when chronic hypoxia reduced fH, Tb, and activity in males but not females. These differences existed without any effect of chronic hypoxia on a-adrenergic or nitric oxide tone on the vasculature (assessed as Pmean 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, fH, Pmean, and Tb 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.

CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner

“…We also observed increased cardiomyocyte injury in male mice, characterized by elevated BNP and ANP levels and increased cardiomyocyte surface area compared to female mice. In line with our findings, Wearing et al reported elevated BNP and ANP levels in male mice [ 46 ]. In addition, it has been demonstrated that a decrease in oxygen pressure led to increased synthesis of natriuretic peptides and that male mice were susceptible to higher cardiac natriuretic peptide levels compared to female mice during myocardial injury [ 47 – 49 ].…”

Evolved reductions in body temperature and the metabolic costs of thermoregulation in deer mice native to high altitude

“…Although plasticity in body temperature is likely adaptive, the plasticity of some other traits can be maladaptive in cold hypoxia. For example, chronic hypoxia can induce prolonged sympathoadrenal activation that leads to systemic hypertension, as observed in some previous studies of lowaltitude humans [69][70][71][72][73][74][75][76][77][78] and rats [79][80][81][82], but not in house mice [47]. Deer mice did not exhibit this pathological response to chronic hypoxia (figure 3), which may have played a role in their ability to colonize high-altitude environments.…”

“…After six weeks of acclimation to warm normoxia or cold hypoxia, deer mice were anaesthetized using isoflurane and surgically instrumented with physiological telemeters (HD-X11, Data Sciences International) using methods we have previously described [47]. Telemetry implants were positioned subcutaneously on the back in the interscapular space for remote measurement of subcutaneous temperature ( T sub ) as a proxy for routine body temperature.…”