title: Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg.
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 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.
authors.affiliation: The Copenhagen Muscle Research Centre, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. stefan.mortensen@rh.regionh.dk
authors.forename: S P
authors.initials: SP
authors.lastname: Mortensen
authors.forename: M
authors.initials: M
authors.lastname: Nyberg
authors.forename: K
authors.initials: K
authors.lastname: Winding
authors.forename: B
authors.initials: B
authors.lastname: Saltin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005263:Femoral Artery / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007866:Leg / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D058473:Receptors, Purinergic P2Y2 / Q000502:physiology; D055815:Young Adult
chemical_list: D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine