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PMID: 15155791 Published · ppublish English Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle.

The Journal of physiology ·Vol. 558 ·No. Pt 1 ·2004-07-01 ·Pages 351-65

Rosenmeier JB, Hansen J, González-Alonso J

Abstract

Despite increases in muscle sympathetic vasoconstrictor activity, skeletal muscle blood flow and O2 delivery increase during exercise in humans in proportion to the local metabolic demand, a phenomenon coupled to local reductions in the oxygenation state of haemoglobin and concomitant increases in circulating ATP. We tested the hypothesis that circulating ATP contributes to local blood flow and O2 delivery regulation by both inducing vasodilatation and blunting the augmented sympathetic vasoconstrictor activity. In eight healthy subjects, we first measured leg blood flow (LBF) and mean arterial pressure (MAP) during three hyperaemic conditions: (1) intrafemoral artery adenosine infusion (vasodilator control), (2) intrafemoral artery ATP infusion (vasodilator), and (3) mild knee-extensor exercise (approximately 20 W), and then compared the responses with the combined infusion of the vasoconstrictor drug tyramine, which evokes endogenous release of noradrenaline from sympathetic nerve endings. In all three hyperaemic conditions, LBF equally increased from approximately 0.5 +/- 0.1 l min(-1) at rest to approximately 3.6 +/- 0.3 l min(-1), with no change in MAP. Tyramine caused significant leg vasoconstriction during adenosine infusion (53 +/- 5 and 56 +/- 5% lower LBF and leg vascular conductance, respectively, P < 0.05), which was completely abolished by both ATP infusion and exercise. In six additional subjects resting in the sitting position, intrafemoral artery infusion of ATP increased LBF and leg vascular conductance 27 +/- 3-fold, despite concomitant increases in venous noradrenaline and muscle sympathetic nerve activity of 2.5 +/- 0.2- and 2.4 +/- 0.1-fold, respectively. Maximal ATP-induced vasodilatation at rest accounted for 78% of the peak LBF during maximal bicycling exercise. Our findings in humans demonstrate that circulating ATP is capable of regulating local skeletal muscle blood flow and O2 delivery by causing substantial vasodilatation and negating the effects of increased sympathetic vasoconstrictor activity.

MeSH Terms
Adenosine/administration & dosage Adenosine Triphosphate/administration & dosage Adult Female Humans Hyperemia/physiopathology Leg/blood supply Male Muscle, Skeletal/blood supply,innervation,physiology Physical Exertion/physiology Rest/physiology Sympathetic Nervous System/physiology Tyramine/administration & dosage Vasoconstriction/drug effects,physiology Vasodilation/drug effects,physiology
Chemicals
Adenosine Triphosphate Adenosine Tyramine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rosenmeier Jaya B
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Hansen Jim
González-Alonso José
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2004.063107
Published
2004-07-01
Epub
2004-00-21
Pages
351-65
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1664919
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.2004.063107 PMC Full Text View journal details
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