Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults

Endothelium-dependent dilatation (EDD) is impaired with ageing in sedentary, but not in regularly exercising adults. We tested the hypotheses that differences in tetrahydrobiopterin (BH 4 ) bioactivity are key mechanisms explaining the impairment in EDD with sedentary ageing, and the maintenance of EDD with ageing in regularly exercising adults. Brachial artery flow-mediated dilatation (FMD), normalized for local shear stress, was measured after acute oral placebo or BH 4 in young sedentary (YS) ( n = 10; 22 ± 1 years, mean ± s.e.m. ), older sedentary (OS) ( n = 9; 62 ± 2), and older habitually aerobically trained (OT) ( n = 12; 66 ± 1) healthy men. At baseline, FMD was ∼50% lower in OS versus YS (1.12 ± 0.09 versus 0.57 ± 0.09 (Δmm (dyn cm −2 )) × 10 −2 , P < 0.001; 1 dyn = 10 −5 N), but was preserved in OT (0.93 ± 0.08 (Δmm (dyn cm −2 )) × 10 −2 ). BH 4 administration improved FMD by ∼45% in OS (1.00 ± 0.10 (Δmm (dyn cm −2 )) × 10 −2 , P < 0.01 versus baseline), but did not affect FMD in YS or OT. Endothelium-independent dilatation neither differed between groups at baseline nor changed with BH 4 administration. These results suggest that BH 4 bioactivity may be a key mechanism involved in the impairment of conduit artery EDD with sedentary ageing, and the EDD-preserving effect of habitual exercise.