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 approximately 50% lower in OS versus YS (1.12 +/- 0.09 versus 0.57 +/- 0.09 (Deltamm (dyn cm(-2))) x 10(-2), P < 0.001; 1 dyn = 10(-5) N), but was preserved in OT (0.93 +/- 0.08 (Deltamm (dyn cm(-2))) x 10(-2)). BH4 administration improved FMD by approximately 45% in OS (1.00 +/- 0.10 (Deltamm (dyn cm(-2))) x 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 BH4 administration. These results suggest that BH4 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.
