Mechanical effects of muscle contraction increase intravascular ATP draining quiescent and active skeletal muscle in humans

Crecelius AR, Kirby BS, Richards JC, Dinenno FA. Mechanical effects of muscle contraction increase intravascular ATP draining quiescent and active skeletal muscle in humans. J Appl Physiol 114: 1085-1093, 2013. First published February 21, 2013; doi:10.1152/japplphysiol.01465.2012.-Intravascular adenosine triphosphate (ATP) evokes vasodilation and is implicated in the regulation of skeletal muscle blood flow during exercise. Mechanical stresses to erythrocytes and endothelial cells stimulate ATP release in vitro. How mechanical effects of muscle contractions contribute to increased plasma ATP during exercise is largely unexplored. We tested the hypothesis that simulated mechanical effects of muscle contractions increase [ATP](venous) and ATP effluent in vivo, independent of changes in tissue metabolic demand, and further increase plasma ATP when superimposed with mild-intensity exercise. In young healthy adults, we measured forearm blood flow (FBF) (Doppler ultrasound) and plasma [ATP](v) (luciferin-luciferase assay), then calculated forearm ATP effluent (FBF x [ATP](v)) during rhythmic forearm compressions (RFC) via a blood pressure cuff at three graded pressures (50, 100, and 200 mmHg; Protocol 1; n = 10) and during RFC at 100 mmHg, 5% maximal voluntary contraction rhythmic handgrip exercise (RHG), and combined RFC + RHG (Protocol 2; n = 10). [ATP](v) increased from rest with each cuff pressure (range 144-161 vs. 64 +/- 13 nmol/l), and ATP effluent was graded with pressure. In Protocol 2, [ATP](v) increased in each condition compared with rest (RFC: 123 +/- 33; RHG: 51 +/- 9; RFC + RHG: 96 +/- 23 vs. Mean Rest: 42 +/- 4 nmol/l; P < 0.05), and ATP effluent was greatest with RFC + RHG (RFC: 5.3 +/- 1.4; RHG: 5.3 +/- 1.1; RFC + RHG: 11.6 +/- 2.7 vs. Mean Rest: 1.2 +/- 0.1 nmol/min; P < 0.05). We conclude that the mechanical effects of muscle contraction can 1) independently elevate intravascular ATP draining quiescent skeletal muscle without changes in local metabolism and 2) further augment intravascular ATP during mild exercise associated with increases in metabolism and local deoxygenation; therefore, it is likely one stimulus for increasing intravascular ATP during exercise in humans.