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

Abstract

Aim: 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).

Methods: We used intact or OVX female rats treated with vehicle or E₂ (0.5 mg/kg/d) and exposed to RA or CIH (21%-10% O₂ , 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.

Results: After 7 or 35 days of CIH, E₂ supplementation reduced arterial pressure. E₂ 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 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 7 days, E₂ supplementation improved the NO-mediated vasodilation. After 35 days of CIH, enzymatic activities, AOPP and aortic reactivity were similar in all groups.

Conclusion: E₂ -based therapy could help prevent the vascular consequences of CIH in apneic women.

Keywords: estradiol; female rats; sleep apnoea; vascular oxidative stress.