Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice

Consumption of a high-fat, high-fructose diet [Western diet (WD)] promotes vascular stiffness, a critical factor in the development of cardiovascular disease (CVD). Obese and diabetic women exhibit greater arterial stiffness than men, which contributes to the increased incidence of CVD in these women. Furthermore, high-fructose diets result in elevated plasma concentrations of uric acid via xanthine oxidase (XO) activation, and uric acid elevation is also associated with increased vascular stiffness. However, the mechanisms by which increased xanthine oxidase activity and uric acid contribute to vascular stiffness in obese females remain to be fully uncovered. Accordingly, we examined the impact of XO inhibition on endothelial function and vascular stiffness in female C57BL/6J mice fed a WD or regular chow for 16 wk. WD feeding resulted in increased arterial stiffness, measured by atomic force microscopy in aortic explants (16.19 ± 1.72 vs. 5.21 ± 0.54 kPa, P < 0.05), as well as abnormal aortic endotheliu...