Tetrahydrobiopterin supplementation enhances carotid artery compliance in healthy older men: a pilot study.
BACKGROUND
We performed a pilot study to test the hypothesis that acute oral ingestion of tetrahydrobiopterin (BH(4)), a key cofactor modulating vascular nitric oxide (NO) synthase activity, improves large elastic artery stiffness with aging in men.


METHODS
Healthy older (63 ± 2 years; n = 8) and young (age 25 ± 1 years; n = 6) men were studied 3 h after ingestion of BH(4) (10 mg·kg(-1) body weight) or placebo on separate days in a randomized, placebo-controlled, double-blind study.


RESULTS
Baseline carotid artery compliance was 37% lower (0.17 ± 0.02 vs. 0.22 ± 0.02 mm/mm Hg·10(-1)) and β-stiffness was 42% higher (7.3 ± 1.1 vs. 4.2 ± 0.5 AU) in the older men (both P < 0.05). BH(4) ingestion markedly increased circulating BH(4) concentrations in both groups (17-19-fold, P < 0.05), but increased compliance (+39% to 0.23 ± 0.02 mm/mm Hg·10(-1), P < 0.01) and decreased β-stiffness index (-27% to 5.3 ± 0.7 AU, P < 0.01) only in the older men. BH(4) also reduced carotid systolic blood pressure (SBP) in the older men (P < 0.05).


CONCLUSIONS
These preliminary results support the possibility that limited BH(4) bioavailability contributes to impaired carotid artery compliance in healthy older men. Further studies are needed to determine if increasing BH(4) bioavailability though oral BH(4) supplementation may have therapeutic efficacy for improving large elastic artery compliance and reducing central SBP with aging.
Department of Integrative Physiology, University of Colorado, Boulder, USA. gary-pierce@uiowa.edu
Gary L
GL
Pierce
Kristen L
KL
Jablonski
Ashley E
AE
Walker
Sara Marian
SM
Seibert
Allison E
AE
DeVan
Stephen M
SM
Black
Shruti
S
Sharma
Douglas R
DR
Seals
D000328:Adult; D000368:Aged; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D003187:Compliance / Q000187:drug effects; D019587:Dietary Supplements; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D059289:Vascular Stiffness / Q000187:drug effects
D001708:Biopterins; C003402:sapropterin