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Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia
Author(s) -
RibonDemars Alexandra,
Pialoux Vincent,
Boreau Anaëlle,
Marcouiller François,
Larivière Richard,
Bairam Aida,
Joseph Vincent
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13159
Subject(s) - ovariectomized rat , endocrinology , medicine , oxidative stress , intermittent hypoxia , catalase , glutathione peroxidase , superoxide dismutase , hypoxia (environmental) , xanthine oxidase , chemistry , vasodilation , estrogen , enzyme , biochemistry , oxygen , obstructive sleep apnea , organic chemistry
Aim We tested the hypothesis that estradiol (E 2 ) 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 E 2 (0.5 mg/kg/d) and exposed to RA or CIH (21%‐10% O 2 , 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 , E 2 supplementation reduced arterial pressure. E 2 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 2 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 2 supplementation improved the NO ‐mediated vasodilation. After 35 days of CIH , enzymatic activities, AOPP and aortic reactivity were similar in all groups. Conclusion E 2 ‐based therapy could help prevent the vascular consequences of CIH in apneic women.