A2 deletion limited HFHS-induced oxidative stress, preserved NO levels and endothelium-dependent vasorelaxation to acetylcholine (ACh). Lipid peroxides are expressed as micromolar of malondialdehyde (MDA) (A), n = 5–9 mice/group, and plasma NO is expressed as picomoles of nitrite (B), n = 5–9 mice/group. Effects of A2 deletion on endothelium-dependent vasorelaxation to acetylcholine (ACh) (C), n = 7–10 mice per group, and sodium nitroprusside (SNP) (D), n = 4–5 mice per group. Values are mean ± SEM. * P < 0.05 when compared to ND-fed mice within the same genotype, # P < 0.05 when compared to WT on the same diet.