title: Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia.
abstract: During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ~60% and ~40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation.
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. mnyberg@ifi.ku.dk
authors.forename: Michael
authors.initials: M
authors.lastname: Nyberg
authors.forename: Baraa K
authors.initials: BK
authors.lastname: Al-Khazraji
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Mortensen
authors.forename: Dwayne N
authors.initials: DN
authors.lastname: Jackson
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Ellis
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001783:Blood Flow Velocity; D002478:Cells, Cultured; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007267:Injections; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D009566:Nitrates; D009573:Nitrites; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate
keywords: microdialysis; nitric oxide; prostanoids; rat gluteus maximus skeletal muscle model