Guinea pig ascorbate status predicts tetrahydrobiopterin plasma concentration and oxidation ratio in vivo.
Tetrahydrobiopterin (BH₄) is an essential co-factor of nitric oxide synthases and is easily oxidized to dihydrobiopterin (BH₂) which promotes endothelial nitric oxide synthase uncoupling and deleterious superoxide production. Vitamin C has been shown to improve endothelial function by different mechanisms, some involving BH₄. The hypothesis of the present study was that vitamin C status, in particular low levels, influences biopterin redox status in vivo. Like humans, the guinea pig lacks the ability to synthesize vitamin C and was therefore used as model. Seven day old animals (n = 10/group) were given a diet containing 100, 250, 500, 750, 1000, or 1500 ppm vitamin C until euthanasia at age 60-64 days. Blood samples were drawn from the heart and analyzed for ascorbate, dehydroascorbic acid (DHA), BH₄ and BH₂ by high-performance liquid chromatography. Plasma BH₄ levels were found to be significantly lower in animals fed 100 ppm vitamin C compared to all other groups (P < .05 or less). BH₂ levels were not significantly different between groups but the BH₂-to-BH₄ ratio was higher in the group fed 100 ppm vitamin C (P < .001 all cases). Significant positive correlations between BH4 and ascorbate and between BH₂-to-BH₄ ratio and DHA were observed (P < .0001 both cases). Likewise, BH₂-to-BH₄ ratio was negatively correlated with ascorbate (P < .0001) as was BH₄ and DHA (P < .005). In conclusion, the redox status of plasma biopterins, essentially involved in vasodilation, depends on the vitamin C status in vivo. Thus, ingestion of insufficient quantities of vitamin C not only leads to vitamin C deficiency but also to increased BH₄ oxidation which may promote endothelial dysfunction.
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Alan
A
Mortensen
Stine
S
Hasselholt
Pernille
P
Tveden-Nyborg
Jens
J
Lykkesfeldt
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000097:blood* / Q000494:pharmacology; D001206:Ascorbic Acid Deficiency / Q000097:blood / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D003683:Dehydroascorbic Acid / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D006168:Guinea Pigs; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D000975:Antioxidants; D001708:Biopterins; C017226:7,8-dihydrobiopterin; C003402:sapropterin; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
Ascorbic acid; BH(2); BH(4); DHA; DTE; Dihydrobiopterin; ED; Guinea pig; HPLC; In vivo oxidation; MPA; NOS; Tetrahydrobiopterin; dehydroascorbic acid; dihydrobiopterin; dithioerythritol; eNOS; endothelial dysfunction; endothelial nitric oxide synthase; high performance liquid chromatography; meta-phosphoric acid; nitric oxide synthase; tetrahydrobiopterin