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

J Physiol. 2012 Dec 1;590(23):6227-36. doi: 10.1113/jphysiol.2012.240093. Epub 2012 Sep 10.


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 VO2 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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Adult
  • Aged
  • Aging / physiology*
  • Endothelium, Vascular / physiopathology
  • Epinephrine / blood
  • Exercise / physiology*
  • Femoral Artery / physiology
  • Humans
  • Hyperemia / physiopathology
  • Leg / physiology*
  • Male
  • Middle Aged
  • Muscle, Skeletal / physiology
  • Norepinephrine / blood
  • Receptors, Purinergic P2Y2 / physiology
  • Young Adult


  • Receptors, Purinergic P2Y2
  • Adenosine Triphosphate
  • Acetylcholine
  • Norepinephrine
  • Epinephrine