Guinea pig ascorbate status predicts tetrahydrobiopterin plasma concentration and oxidation ratio in vivo

TY - JOUR

T1 - Guinea pig ascorbate status predicts tetrahydrobiopterin plasma concentration and oxidation ratio in vivo

AU - Mortensen, Alan

AU - Andersen, Stine Hasselholt

AU - Tveden-Nyborg, Pernille

AU - Lykkesfeldt, Jens

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - Ascorbic acid

KW - Tetrahydrobiopterin

KW - Dihydrobiopterin

KW - Guinea pig

KW - In vivo oxidation

U2 - 10.1016/j.nutres.2013.07.006

DO - 10.1016/j.nutres.2013.07.006

M3 - Journal article

C2 - 24074744

SN - 0271-5317

VL - 33

SP - 859

EP - 867

JO - Nutrition Research

JF - Nutrition Research

IS - 10

ER -