Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia.

Abstract

We tested the hypothesis that estradiol (E2 ) 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 E2 (0.5mg/kg/d) and exposed to RA or CIH (21%-10% O2 , 10cycles/h, 8h/d) for 7 or 35days, 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 35days of CIH, E2 supplementation reduced arterial pressure. E2 reduced plasma endothelin-1 levels after 7days of CIH, but not after 35days. Ovariectomy, but not CIH for 7days, increased aortic oxidative stress and E2 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 7days, E2 supplementation improved the NO-mediated vasodilation. After 35days of CIH, enzymatic activities, AOPP and aortic reactivity were similar in all groups. E2 -based therapy could help prevent the vascular consequences of CIH in apneic women.