Role of Aging Versus the Loss of Estrogens in the Reduction in Vascular Function in Female Rats

Abstract

Although aging is known to lead to increased vascular stiffness, the role of estrogens in the prevention of age-related changes in the vasculature remains to be elucidated. To address this, we measured vascular function in the thoracic aorta in adult and old ovariectomized (ovx) rats with and without immediate 17β-estradiol (E2) replacement. In addition, aortic mRNA and protein were analyzed for proteins known to be involved in vasorelaxation. Aging in combination with the loss of estrogens led to decreased vasorelaxation in response to acetylcholine and sodium nitroprusside, indicating either smooth muscle dysfunction and/or increased fibrosis. Loss of estrogens led to increased vascular tension in response to phenylephrine, which could be partially restored by E2 replacement. Levels of endothelial nitric oxide synthase and inducible nitric oxide synthase did not differ among the groups, nor did total nitrite plus nitrate levels. Old ovx exhibited decreased expression of both the α and β-subunits of soluble guanylyl cyclase (sGC) and had impaired nitric oxide signaling in the vascular smooth muscle. Immediate E2 replacement in the aged ovx prevented both the impairment in vasorelaxation, and the decreased sGC receptor expression and abnormal sGC signaling within the vascular smooth muscle. The combination of loss of estradiol and aging leads to increased constriction (phenylephrine) and decreased relaxation with nitric oxide. Reduced soluble guanylyl cyclase mediates these changes.