Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada.
Laboratoire Inter-Universitaire de biologie de la motricité, Université Claude Bernard Lyon1, Villeurbanne, France.
Acta Physiol (Oxf). 2019 Feb;225(2):e13159. doi: 10.1111/apha.13159. Epub 2018 Jul 17.
We tested the hypothesis that estradiol (E ) reduces aortic oxidative stress and endothelial dysfunction in ovariectomized (OVX) female rats exposed to room air (RA) or chronic intermittent hypoxia (CIH).
We used intact or OVX female rats treated with vehicle or E (0.5 mg/kg/d) and exposed to RA or CIH (21%-10% O , 10 cycles/h, 8 h/d) for 7 or 35 days, and measured the arterial pressure, heart rate and plasma endothelin-1 levels. We also measured in thoracic aortic samples, the activities of the pro-oxidant enzymes NADPH (NOX) and xanthine oxidase (XO), the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and the advanced oxidation protein products (AOPP-oxidative stress marker). Finally, we used aortic rings to assess the contractile response to phenylephrine and the vasodilatory response to acetylcholine.
After 7 or 35 days of CIH, E supplementation reduced arterial pressure. E reduced plasma endothelin-1 levels after 7 days of CIH, but not after 35 days. Ovariectomy, but not CIH for 7 days, increased aortic oxidative stress and E treatment prevented this effect. Remarkably, in animals exposed to RA, this was achieved by a reduction in NOX and XO activities, but in animals exposed to CIH this was achieved by increased catalase activity. In OVX female rats exposed to CIH for 7 days, E supplementation improved the NO-mediated vasodilation. After 35 days of CIH, enzymatic activities, AOPP and aortic reactivity were similar in all groups.
E -based therapy could help prevent the vascular consequences of CIH in apneic women.
我们检验了这样一个假设，即雌二醇（E）可降低暴露于常氧（RA）或慢性间歇性低氧（CIH）环境中的去卵巢（OVX）雌性大鼠的主动脉氧化应激和内皮功能障碍。
我们使用完整或 OVX 雌性大鼠，用载体或 E（0.5mg/kg/d）处理，并暴露于 RA 或 CIH（21%-10%O 2 ，10 个循环/小时，8 小时/天）7 或 35 天，并测量动脉压、心率和血浆内皮素-1 水平。我们还测量了胸主动脉样本中促氧化剂酶 NADPH（NOX）和黄嘌呤氧化酶（XO）、抗氧化酶超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和晚期氧化蛋白产物（AOPP-氧化应激标志物）的活性。最后，我们使用主动脉环评估对苯肾上腺素的收缩反应和乙酰胆碱的舒张反应。
CIH 后 7 或 35 天，E 补充降低了动脉压。E 降低了 CIH 后 7 天的血浆内皮素-1 水平，但 35 天后没有降低。OVX 本身，而不是 7 天的 CIH，增加了主动脉氧化应激，而 E 治疗则阻止了这种效应。值得注意的是，在暴露于 RA 的动物中，这是通过降低 NOX 和 XO 活性来实现的，但在暴露于 CIH 的动物中，这是通过增加过氧化氢酶活性来实现的。在 CIH 暴露 7 天的 OVX 雌性大鼠中，E 补充改善了 NO 介导的血管舒张。CIH 后 35 天，所有组的酶活性、AOPP 和主动脉反应性均相似。
E 为基础的治疗可能有助于预防 CIH 对呼吸暂停女性的血管后果。
