Conjugated equine estrogen treatment corrected the exacerbated aorta oxidative stress in ovariectomized spontaneously hypertensive rats

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Abstract

Objective

The increased risk of cardiovascular diseases in postmenopausal women has been linked to the decrease in plasma estrogen levels. Preparation of conjugate equine estrogens (CEE) is one of the most routinely used hormone therapy in postmenopausal women. However, studies on the vascular effects of CEE are still sparse and the mechanism of action is not completely elucidated. In this context, we have determined the effects of CEE in the vascular oxidative stress observed in ovariectomyzed (OVX) spontaneously hypertensive rats (SHR). Mechanisms by which CEE interferes with redox-sensitive pathways and endothelial function were also determined.

Results

Aortas from OVX rats exhibited increased generation of reactive oxygen species (ROS), NADPH oxidase activity and reduced catalase protein expression, compared to aortas from sham SHR. Endothelium-intact aortic rings from OVX were hyperreactive to NE when compared to Sham aortas. This hyperreactivity was corrected by superoxide dismutase (SOD), catalase, and endothelium removal. Treatment of OVX-SHR with CEE reduced vascular ROS generation, NADPH oxidase activity, enhanced SOD and catalase expression and also corrected the NE-hyperreactivity in aortic rings from OVX-SHR.

Conclusion

Our study indicates a potential benefit of CEE therapy through a mechanism that involves reduction in oxidative stress, improving endothelial function in OVX hypertensive rats.

Highlights

★ Ovariectomized hypertensive rats (OVX) were treated with conjugate equine estrogens (CEE). ★ CEE prevented aorta reactive oxygen species increased generation. ★ CEE prevented NADPH activation and increased antioxidant enzymes expression. ★ CEE corrected norepinephrine hyperreactivity in aortic endothelium-intact rings. ★ CEE improved endothelial function in OVX aorta.

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