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

TitleRoles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats.
Publication TypeJournal Article
Year of Publication2019
AuteursLaouafa, S, Roussel, D, Marcouiller, F, Soliz, J, Gozal, D, Bairam, A, Joseph, V
JournalActa Physiol (Oxf)
Paginatione13255
Date Published2019 Jan 11
ISSN1748-1716
Abstract

AIM: Chronic intermittent hypoxia (CIH) induces systemic (hypertension) and central alterations (mitochondrial dysfunction underlying cognitive deficits). We hypothesized that agonists of oestradiol receptors (ER) α and β prevent CIH-induced hypertension and brain mitochondrial dysfunction.METHODS: Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh), the ERα agonist propylpyraoletriol (PPT - 30 μg/kg/day) or the ERβ agonist diarylpropionitril (DPN - 100 μg/kg/day). Animals were exposed to CIH (21%-10% F O - 10 cycles/hour - 8 hours/day - 7 days) or normoxia. Arterial blood pressure was measured after CIH or normoxia exposures. Mitochondrial respiration and H O 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).RESULTS: Propylpyraoletriol but not DPN prevented the rise of arterial pressure induced by CIH. CIH exposures decreased O consumption, complex I activity, and increased H O 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.CONCLUSIONS: We conclude that in OVX female rats, the ERα agonist prevents from CIH-induced hypertension while both ERα and ERβ 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.

DOI10.1111/apha.13255
Alternate JournalActa Physiol (Oxf)
PubMed ID30635990
Grant ListMOP-102715 / / Canadian Institutes of Health Research / Canada
MOP-119272 / / Canadian Institutes of Health Research / Canada
HL130984 / / National Institutes of Health /
R01 HL130984 / HL / NHLBI NIH HHS / United States
R56 HL140548 / HL / NHLBI NIH HHS / United States