Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle.
Level 3 - non-randomized controlled study
Non-randomized within-subject experimental physiological study in humans
PubMed 18703581 · doi:10.1113/jphysiol.2008.155432
What was done
In nine healthy males, investigators infused adenosine, AMP, ADP, ATP, or UTP into the intrafemoral artery at rest. They compared the nucleotide doses required to elevate leg blood flow from approximately 0.5 l min(-1) at baseline to approximately 3.5 l min(-1) and tested the ability of each compound to blunt vasoconstriction during co-infusion with the sympathetic vasoconstrictor tyramine. Measured outcomes included leg blood flow, mean arterial pressure, cardiac output, leg arterial-venous O2 difference, plasma ATP, and soluble nucleotidase activities.
What was found
The relative vasoactive potency rank order was ATP (100) = UTP (100) >> adenosine (5.8) > ADP (2.7) > AMP (1.7). Infusions caused no shifts in plasma ATP or soluble serum nucleotidase activities. Tyramine increased plasma noradrenaline in all conditions, but leg vasoconstriction occurred only during infusions of adenosine (leg blood flow decreased from 3.2 ± 0.3 to 1.8 ± 0.2 l min(-1)), AMP (3.7 ± 0.4 to 1.7 ± 0.2 l min(-1)), and ADP (3.3 ± 0.4 to 2.4 ± 0.3 l min(-1); all P < 0.05), whereas ATP and UTP blunted this vasoconstriction.
Why it matters
The study demonstrates that ATP-mediated vasodilation and functional sympatholysis in human skeletal muscle occur through direct stimulation of ATP/UTP-selective receptors rather than through downstream dephosphorylation to adenosine.
Limits
The sample was limited to nine healthy males, preventing direct generalization to females, older populations, or clinical cohorts. Exogenous intra-arterial pharmacological infusion at rest may not fully replicate endogenous nucleotide release patterns during exercise.
Cited by
- supports During intense dynamic exercise, red blood cells, blood vessels, and skeletal muscle release ATP and ADP, which act as potent vasodilators causing local functional sympatholysis.