Alexandra Ribon-Demars1,2, Vincent Pialoux2,3, Anaëlle Boreau2, François Marcouiller1, Richard Larivière4, Aida Bairam1, Vincent Joseph1. 1. Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada. 2. Laboratoire Inter-Universitaire de biologie de la motricité, Université Claude Bernard Lyon1, Villeurbanne, France. 3. Institut Universitaire de France, Paris, France. 4. Centre de Recherche du Centre Hospitalier, Universitaire de Québec, Hôtel-Dieu de Québec, Université Laval, Québec, QC, Canada.
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.
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.
Authors: Dain W Jacob; Elizabeth P Ott; Sarah E Baker; Zachariah M Scruggs; Clayton L Ivie; Jennifer L Harper; Camila M Manrique-Acevedo; Jacqueline K Limberg Journal: Am J Physiol Regul Integr Comp Physiol Date: 2020-09-23 Impact factor: 3.619
Authors: François Marcouiller; Alexandra Jochmans-Lemoine; Gauthier Ganouna-Cohen; Mathilde Mouchiroud; Mathieu Laplante; André Marette; Aida Bairam; Vincent Joseph Journal: Am J Physiol Endocrinol Metab Date: 2020-12-07 Impact factor: 4.310
Authors: Abdulaziz A Alzahrani; Lily L Cao; Hayyaf S Aldossary; Demitris Nathanael; Jiarong Fu; Clare J Ray; Keith L Brain; Prem Kumar; Andrew M Coney; Andrew P Holmes Journal: Pflugers Arch Date: 2020-11-19 Impact factor: 3.657