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INTEGRATIVE |
-adrenergic vasoconstriction in the human forearm: implications for vascular control in contracting muscle
1 Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523-1582, USA
2
Heart Center of the Rockies, Poudre Valley Health System, Fort Collins, CO 80528, USA
Recent evidence suggests that adenosine triphosphate (ATP) can inhibit vasoconstrictor responses to endogenous noradrenaline release via tyramine in the skeletal muscle circulation, similar to what is observed in contracting muscle. Whether this involves direct modulation of postjunctional 
-adrenoceptor responsiveness, or is selective for 1- or 2-receptors remains unclear. Therefore, in Protocol 1, we tested the hypothesis that exogenous ATP can blunt direct postjunctional -adrenergic vasoconstriction in humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses to local intra-arterial infusions of phenylephrine (1-agonist) and dexmedetomidine (2-agonist) during moderate rhythmic handgrip exercise (15% maximum voluntary contraction), during a control non-exercise vasodilator condition (adenosine), and during ATP infusion in eight young adults. Forearm hyperaemia was matched across all conditions. Forearm vasoconstrictor responses to direct 1-receptor stimulation were blunted during exercise versus adenosine (
FVC = –11 ± 3% versus –39 ± 5%; P< 0.05), and were abolished during ATP infusion (–3 ± 2%). Similarly, vasoconstrictor responses to 2-receptor stimulation were blunted during exercise versus adenosine (–13 ± 4% versus –40 ± 8%; P< 0.05), and were abolished during ATP infusion (–4 ± 4%). In Prototol 2 (n = 10), we tested the hypothesis that graded increases in ATP would reduce 1-mediated vasoconstriction in a dose-dependent manner compared with vasodilatation evoked via adenosine. Forearm vasoconstrictor responses during low dose adenosine (–38 ± 3%) and ATP (–33 ± 2%) were not significantly different from rest (–40 ± 3%; P> 0.05). In contrast, vasoconstrictor responses during moderate (–22 ± 6%) and high dose ATP (–8 ± 5%) were significantly blunted compared with rest, whereas the responses during adenosine became progressively greater (moderate = –48 ± 4%, P = 0.10; high = –53 ± 6%, P< 0.05). We conclude that exogenous ATP is capable of blunting direct postjunctional -adrenergic vasoconstriction, that this involves both 1- and 2-receptor subtypes, and that this is graded with ATP concentrations. Collectively, these data are consistent with the conceptual framework regarding how muscle blood flow and vascular tone are regulated in contracting muscles of humans.
(Received 19 March 2008;
accepted after revision 8 July 2008;
first published online 10 July 2008)
Corresponding author F. A. Dinenno: Department of Health and Exercise Science, Colorado State University, 220 Moby-B Complex, Fort Collins, CO 80523-1582, USA. Email: fdinenno{at}cahs.colostate.edu
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