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Key points

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    Ageing is associated with a reduced exercise hyperaemia and impaired ability to override sympathetic vasoconstrictor activity (functional sympatholysis).
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    We find that sedentary elderly have a lower vasodilator response to ACh and ATP in the leg compared to young, but also that this age-related reduction is partially (ACh) or completely (ATP) offset in lifelong physically active elderly subjects.
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    An increase in sympathetic vasoconstrictor activity induced by tyramine reduces exercise hyperaemia in sedentary elderly, but not active elderly and young subjects.
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    Interstitial ATP levels during exercise and P2Y2 receptor content are more related to the physical activity level than age.
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    Physical activity can prevent the age-related impairment in functional sympatholysis and maintain a sufficient O2 delivery during moderate intensity exercise despite a loss of endothelial function.

Abstract  Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y2 receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2 years) men at rest and during one-legged knee extensions (12 W and 45% maximal workload (WLmax)) and arterial infusion of ACh and ATP with and without tyramine. The vasodilatory response to ACh was lowest in the sedentary elderly, higher in active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP-induced vasodilatation was lower in the sedentary elderly (P < 0.05). During exercise (12 W), leg blood flow, vascular conductance and inline image was lower and leg lactate release higher in the sedentary elderly compared to the young (P < 0.05), whereas there was no difference between the active elderly and young. Interstitial [ATP] during exercise and P2Y2 receptor content were higher in the active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion lowered resting vascular conductance in all groups, but only in the sedentary elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P < 0.05). A lifelong physically active lifestyle can maintain an intact functional sympatholysis during exercise and vasodilator response to ATP despite a reduction in endothelial nitric oxide function. A physically active lifestyle increases interstitial ATP levels and skeletal muscle P2Y2 receptor content.