Progesterone prevents oxidative stress and respiratory dysfunctions in female rats exposed to intermittent hypoxia.

Abstract

The occurrence of sleep apnea (SA) increases after menopause in women, which is partly related to the decreased levels of ovarian hormones. Because progesterone (Prog) is a neuroprotective hormone and a potent respiratory stimulant, we tested the hypothesis that Prog reduces the apnea frequency and the oxidative stress induced by IH. We used OVX female rats implanted with an osmotic pump delivering vehicle (OVX‐Veh) or prog (4mg/kg/day). Two weeks following the surgery, rats were exposed to room air (RA), or IH for 7 days (nadir 10% O2, 10 cycles/hour, 8 hours/day). We studied three groups: OVX‐Veh‐RA; OVX‐Veh‐IH; and OVX‐Prog‐IH. At the end of exposure period, we measured the mean arterial pressure (tail cuff) and assessed the frequency of apneas during sleep and the ventilatory responses to hypoxia using whole body plethysmography. The brain was quickly harvested to measure the activity of the pro‐oxidant enzyme NADPH oxidase (NOX), and the antioxidant enzymes (mitochondrial and cytosolic superoxide dismutase ‐ SOD) in the cerebral cortex and brainstem. IH exposure increased the mean arterial blood pressure, the frequency of apneas during sleep, and the hypoxic ventilatory response. Prog did not prevent the elevation of blood pressure, but effectively reduced the frequency of apneas during sleep and prevented the elevation of the hypoxic ventilatory response. In the cerebral cortex, IH increased NOX activity, and decreased the activity of the cytosolic and mitochondrial SOD, these effects were prevented by Prog. None of these enzyme activities were altered by IH or Prog supplementation in the brainstem. We conclude that Prog prevents the respiratory alterations induced by IH, and reduces oxidative stress in the brain cortex. These studies are useful to better understand the responses to IH and sleep apnea in women particularly after menopause.Support or Funding InformationSupported by CIHR.