Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

AimChronic intermittent hypoxia (CIH) induces systemic (hypertension) and central alterations (mitochondrial dysfunction underlying cognitive deficits). We hypothesized that agonists of oestradiol receptors (ER) and prevent CIH-induced hypertension and brain mitochondrial dysfunction. MethodsOvariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh), the ER agonist propylpyraoletriol (PPT 30g/kg/day) or the ER agonist diarylpropionitril (DPN 100g/kg/day). Animals were exposed to CIH (21%-10% FIO2 10 cycles/hour - 8hours/day - 7days) or normoxia. Arterial blood pressure was measured after CIH or normoxia exposures. Mitochondrial respiration and H2O2 production were measured in brain cortex with high-resolution respirometry, as well as activity of complex I and IV of the electron transport chain, citrate synthase, pyruvate, and lactate dehydrogenase (PDH and LDH). ResultsPropylpyraoletriol but not DPN prevented the rise of arterial pressure induced by CIH. CIH exposures decreased O-2 consumption, complex I activity, and increased H2O2 production. CIH had no effect on citrate synthase activity, but decreased PDH activity and increased LDH activity indicating higher anaerobic glycolysis. Propylpyraoletriol and DPN treatments prevented all these alterations. ConclusionsWe conclude that in OVX female rats, the ER agonist prevents from CIH-induced hypertension while both ER and ER agonists prevent the brain mitochondrial dysfunction and metabolic switch induced by CIH. These findings may have implications for menopausal women suffering of sleep apnoea regarding hormonal therapy.