Muscle interstitial norepinephrine and nucleotides during exercise and arterial ATP infusion

Plasma ATP has been suggested to play a role in the skeletal muscle hyperaemia during muscle contractions, while interstitial ATP may contribute to the increase sympathetic nerve activity, by stimulating muscle afferents. We measured leg hemodynamics and muscle interstitial NE, ATP, ADP, AMP and adenosine during intra‐arterial ATP infusion (0.42±0.04 and 2.26±0.52 μmol min −1 ;mean±SEM) and one‐legged knee extensor exercise (18±1 and 37±1W) in 7 healthy, male subjects (24±2 years, 76±3 kg). ATP infusion increased leg blood flow (LBF) from 0.4±0.0 l min −1 at baseline to 2.8±0.3 (0.42 μmol ATP min −1 ) and 4.5±0.4 (2.26 μmol ATP min −1 ) l min −1 , while LBF during exercise increased from 0.4±0.1 at rest to 3.6±0.3 (18W) and 4.9±0.5 (37W) l min −1 . Interstitial [NE] remained unchanged during the low ATP infusion (0.5±0.2 and 0.7±0.1 μM at baseline and ATP infusion, respectively), but increased to 2.0±0.5μM during the high ATP infusion rate, while [ATP], [ADP], [AMP] and [ADO] remained unchanged during both ATP infusions. Exercise increased interstitial [NE], [ATP], [ADP], [AMP] and [ADO] from 0.5±0.0, 2.0±0.7, 0.06±0.01, 0.06±0.01, 0.2±0.0 and 0.1±0.0 μM, respectively, to 2.9±0.7, 5.61±1.25, 4.80±1.30, 4.1±1.7 and 0.8±0.0 μM, respectively ( P< 0.05). These results indicate that ATP in plasma exerts its vasodilatory effects directly on the endothelium as arterially infused ATP and its breakdown products do not appear to reach the interstitium. Furthermore, the relationship between interstitial NE and ATP suggests that ATP may play a role in the increased sympathetic nerve activity observed during exercise. Supported by Lundbeck Foundation