Document Detail

Sources of intravascular ATP during exercise in humans: critical role for skeletal muscle perfusion.
MedLine Citation:
PMID:  23315195     Owner:  NLM     Status:  MEDLINE    
Exercise hyperaemia is regulated by several factors, and one factor known to increase with exercise that evokes a powerful vasomotor action is extracellular ATP. The origin of ATP detected in plasma from exercising muscle of humans is, however, a matter of debate, and ATP has been suggested to arise from sympathetic nerves, blood sources (e.g. erythrocytes), endothelial cells and skeletal myocytes, among others. Therefore, we tested the hypothesis that acute augmentation of sympathetic nervous system activity (SNA) results in elevated plasma ATP draining skeletal muscle, and that SNA superimposition during exercise increases ATP more than exercise alone. We showed that increased SNA via -40 mmHg lower body negative pressure (LBNP) at rest did not increase plasma ATP (51±8 nmol l(-1) at rest versus 58±7 nmol l(-1) with LBNP), nor did it increase [ATP] above levels observed during rhythmic hand-grip exercise (79±11 nmol l(-1) with exercise alone versus 71±8 nmol l(-1) with LBNP). Next, we tested the hypothesis that active perfusion of skeletal muscle is essential to observe increased plasma ATP during exercise. We showed that complete obstruction of blood flow to contracting muscle abolished exercise-mediated increases in plasma ATP (from 90±19 to 49±12 nmol l(-1)), and that cessation of blood flow prior to exercise completely inhibited the typical rise in ATP (3 versus 61%, obstructed versus intact perfusion). The lack of change in ATP during occlusion occurred in the face of continued muscular work and elevated SNA, indicating that the rise of intravascular ATP did not result from these extravascular sources. Our collective observations indicated that the elevation in extracellular ATP observed in blood during exercise was unlikely to originate from sympathetic nerves or the contacting muscle itself, but rather was dependent on intact skeletal muscle perfusion. We conclude that an intravascular source for ATP is essential, which indicates an important role for blood sources (e.g. red blood cells) in augmenting and maintaining elevated plasma ATP during exercise.
Brett S Kirby; Anne R Crecelius; Jennifer C Richards; Frank A Dinenno
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-11
Journal Detail:
Title:  Experimental physiology     Volume:  98     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-11-11     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  988-98     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / blood*
Carbon Dioxide / blood
Exercise / physiology*
Forearm / physiology
Hand Strength
Muscle Contraction / physiology
Muscle, Skeletal / blood supply*,  physiology
Oxygen / blood
Sympathetic Nervous System / physiology
Young Adult
Grant Support
Reg. No./Substance:
142M471B3J/Carbon Dioxide; 8L70Q75FXE/Adenosine Triphosphate; S88TT14065/Oxygen

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