Impaired Modulation of Sympathetic Alpha-adrenergic Vasoconstriction in Contracting Forearm Muscle of Ageing Men

Recent evidence indicates that older healthy humans demonstrate greater vasoconstrictor tone in their active muscles during exercise compared with young adults. Therefore, we tested the hypothesis that the normal ability of muscle contractions to blunt sympathetic alpha-adrenergic vasoconstriction (functional sympatholysis) is impaired with age in healthy humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated the forearm vascular conductance (FVC) responses to alpha-adrenergic receptor stimulation during rhythmic handgrip exercise (15% maximum voluntary contraction) and during a control non-exercise vasodilator condition (intra-arterial adenosine infusion) in seven young (25 +/- 2 years) and eight healthy older men (65 +/- 2 year). FVC responses to intra-arterial tyramine (evokes endogenous noradrenaline release), phenylephrine (alpha1-agonist) and clonidine (alpha2-agonist) were assessed. In young men, the vasoconstrictor responses to tyramine (-25 +/- 1 versus -56 +/- 6%), phenylephrine (-11 +/- 4 versus -39 +/- 4%) and clonidine (-12 +/- 4 versus -38 +/- 5%; all P < 0.005) were blunted during exercise compared with adenosine. In contrast, exercise did not significantly blunt the response to tyramine (-30 +/- 2 versus -36 +/- 7%; P = 0.4) or phenylephrine (-16 +/- 2 versus -19 +/- 3%; P = 0.3) in older men, but did attenuate the response to clonidine (-22 +/- 3 versus -37 +/- 6%; P < 0.05). The magnitude of functional sympatholysis, calculated as the difference in the vasoconstrictor responses during adenosine infusion and exercise, was significantly lower in older compared with young men in the presence of tyramine (-6 +/- 7 versus -31 +/- 6%), phenylephrine (-3 +/- 3 versus -28 +/- 4%) and clonidine (-15 +/- 4 versus -26 +/- 3%; all P < 0.05). We conclude that ageing is associated with impaired functional sympatholysis in the vascular beds of contracting forearm muscle in healthy men. These findings might help explain the greater skeletal muscle vasoconstrictor tone and reduced blood flow during large muscle dynamic exercise in older adults.