Age- and Sex-Specific Effects of Tetrahydrobiopterin Supplementation on Peripheral Artery Stiffness

Open Access
Comer, Carly Diana
Area of Honors:
Interdisciplinary in Biology and Kinesiology
Bachelor of Science
Document Type:
Thesis Supervisors:
  • David Nathan Proctor, Thesis Supervisor
  • Stephen Jacob Piazza, Honors Advisor
  • Stephen Wade Schaeffer, Honors Advisor
  • arterial stiffness
  • pressure-strain elastic modulus
  • brachial artery
  • common femoral artery
  • tetrahydrobiopterin
Objective: To compare the elastic properties of peripheral arteries in healthy older (vs. younger) men and women and to determine if acute administration of tetrahydrobiopterin (BH4, a substance that increases bioavailability of the vasodilator nitric oxide) alters these properties in a sex-specific manner. Methods: Resting diameter of the brachial and common femoral arteries (Doppler ultrasound) and blood pressure (Finometer) were measured in 13 men (6 younger, 7 older) and 16 women (7 younger, 9 older). Pressure-strain elastic modulus (Ep) and stiffness index (β), as well as the two determinants of Ep, pulse pressure (PP) and relative diameter change (%), were evaluated under resting conditions following randomized oral administration of placebo or BH4 (10 mg/kg body weight) on separate visits. Results: Under the placebo condition, aside from younger women having a lower PP (p ≤ 0.05) than older women, there were no age or sex differences in any of the elastic properties measured. Under the BH4 condition, no effect on arterial distensibility was observed in men (younger or older) or younger women. Older women, by contrast, exhibited BH4-induced reductions in the Ep of both arteries, and a reduction in stiffness (β) of their brachial artery (all p ≤ 0.05), resulting in older women having significantly more distensible arteries in the presence of BH4 than younger women. Conclusions: There is an age dependent effect of acute BH4 administration (10 mg/kg) on the distensibility of peripheral arteries in women, but not men. The increase in peripheral (muscular) artery distensibility observed in older women following BH4 administration could reflect a reversal of vascular endothelial dysfunction (i.e. decreased endothelium-dependent vasodilation) that healthy women typically experience as they age.