Reduced superoxide production and increased NO production in aortas by BH4 supplementation in apoE-KO/eNOS-Tg mice. (a) Quantitative analysis of superoxide production in both nonplaque and plaque areas in BH4-treated (black bars) and untreated apoE-KO/eNOS-Tg mice (white bars). BH4 administration significantly decreased superoxide production in plaque areas in apoE-KO/eNOS-Tg. n = 6–10 for each group. *P < 0.01 vs. plaque areas in untreated apoE-KO/eNOS-Tg mice. (b) Effects of BH4 on the superoxide production in the endothelium. Removal of the endothelium reduced superoxide levels in both nonplaque and plaque areas; however, the degree of the reduction was significantly attenuated in nonplaque areas by BH4 treatment. *P < 0.05 vs. nonplaque areas in untreated apoE-KO/eNOS-Tg mice. (c) Effects of BH4 on NO production in aortas. Acetylcholine-stimulated NO production was significantly increased by BH4 supplementation in apoE-KO/eNOS-Tg mice. n = 6 for both groups. *P < 0.05 vs. untreated apoE-KO/eNOS-Tg mice.