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

Abstract

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.

Figure 1

Brachial artery flow-mediated dilatation (FMD) (top panel) and endothelium-independent dilatation (bottom panel) in young sedentary (black bars) and older sedentary (white bars) and regularly exercising (grey bars) healthy men after acute oral placebo (baseline conditions) or tetrahydrobiopterin (BH₄) supplementation. FMD values are normalized for the stimulus. Mean ± s.e.m. values are shown. *P < 0.001 versus young and older exercising men. †P < 0.01 versus placebo condition.