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• W1577903510 abstract "Sympathetic vasoconstriction is blunted in the vascular beds of contracting skeletal muscle in humans, presumably due to the action of vasoactive metabolites (functional sympatholysis). Recently, we demonstrated that infusion of ATP into the arterial circulation of the resting human leg increases blood flow and concomitantly blunts α-adrenergic vasoconstriction in a similar manner to that during moderate exercise. Here we tested the hypothesis that ATP, rather than its dephosphorylated metabolites, induces vasodilatation and sympatholysis in resting skeletal muscle via activation of ATP/UTP-selective receptors. To this aim, we first measured leg blood flow (LBF), mean arterial pressure (MAP), cardiac output , leg arterial–venous (a–v) O2 difference, plasma ATP and soluble nucleotidase activities during intrafemoral artery infusion of adenosine, AMP, ADP, ATP or UTP in nine healthy males. Comparison of the doses of nucleotides and adenosine required for a similar increase in LBF from ∼0.5 l min−1 at baseline to ∼3.5 l min−1 (without altering MAP but increasing significantly) revealed the following rank order of vasoactive potency: ATP (100) = UTP (100) >> adenosine (5.8) > ADP (2.7) > AMP (1.7). The infusions did not cause any shifts in plasma ATP level or soluble serum nucleotidase activities. Combined infusion of the vasodilatory compounds and the sympathetic vasoconstrictor drug tyramine increased plasma noradrenaline in all hyperaemic conditions, but only caused leg and systemic vasoconstriction and augmented O2 extraction during adenosine, AMP and ADP infusion (LBF from 3.2 ± 0.3 to 1.8 ± 0.2 l min−1; 3.7 ± 0.4 to 1.7 ± 0.2 l min−1 and 3.3 ± 0.4 to 2.4 ± 0.3 l min−1, respectively, P < 0.05). These findings in humans suggest that the vasodilatory and sympatholytic effects of exogenous ATP in the skeletal muscle vasculature are largely mediated via ATP itself rather than its dephosphorylated metabolites, most likely via binding to endothelial ATP/UTP-selective P2Y2 receptors. These data are consistent with a role of ATP in skeletal muscle hyperaemia in conditions of increased sympathetic nerve drive such as exercise or hypoxia." @default.
• W1577903510 created "2016-06-24" @default.
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• W1577903510 date "2008-10-14" @default.
• W1577903510 modified "2023-10-02" @default.
• W1577903510 title "Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle" @default.
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• W1577903510 doi "https://doi.org/10.1113/jphysiol.2008.155432" @default.
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