Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada.
CNRS, UMR 5023, Université Claude Bernard Lyon 1, Villeurbanne, France.
Acta Physiol (Oxf). 2019 Jun;226(2):e13255. doi: 10.1111/apha.13255. Epub 2019 Jan 30.
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.
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).
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.
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.
慢性间歇性低氧（CIH）引起全身（高血压）和中枢（认知功能障碍相关的线粒体功能障碍）改变。我们假设雌激素受体（ER）α和β激动剂可预防 CIH 引起的高血压和脑线粒体功能障碍。
将去卵巢雌性大鼠植入渗透泵，以输送载体（Veh）、ERα激动剂丙基吡罗醇（PPT-30μg/kg/天）或 ERβ激动剂二芳基丙腈（DPN-100μg/kg/天）。动物暴露于 CIH（21%-10%F O-10 个循环/小时-8 小时/天-7 天）或常氧。在 CIH 或常氧暴露后测量动脉血压。用高分辨率呼吸仪测量大脑皮质的线粒体呼吸和 H2O 产生，以及电子传递链复合物 I 和 IV、柠檬酸合酶、丙酮酸和乳酸脱氢酶（PDH 和 LDH）的活性。
丙基吡罗醇但不是 DPN 预防了 CIH 引起的动脉压升高。CIH 暴露降低了 O 消耗、复合物 I 活性并增加了 H2O 产生。CIH 对柠檬酸合酶活性没有影响，但降低了 PDH 活性并增加了 LDH 活性，表明无氧糖酵解增加。丙基吡罗醇和 DPN 治疗预防了所有这些变化。
我们得出结论，在去卵巢雌性大鼠中，ERα 激动剂可预防 CIH 引起的高血压，而 ERα 和 ERβ 激动剂均可预防 CIH 引起的脑线粒体功能障碍和代谢转换。这些发现可能对患有睡眠呼吸暂停的更年期妇女的激素治疗具有重要意义。
