Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg

Key points Ageing is associated with a reduced exercise hyperaemia and impaired ability to override sympathetic vasoconstrictor activity (functional sympatholysis). 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. An increase in sympathetic vasoconstrictor activity induced by tyramine reduces exercise hyperaemia in sedentary elderly, but not active elderly and young subjects. Interstitial ATP levels during exercise and P2Y 2 receptor content are more related to the physical activity level than age. Physical activity can prevent the age‐related impairment in functional sympatholysis and maintain a sufficient O 2 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 P2Y 2 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 (WL max )) 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 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 P2Y 2 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 P2Y 2 receptor content.