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J Physiol Volume 579, Number 1, 237-245, February 15, 2007 DOI: 10.1113/jphysiol.2006.123000
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SKELETAL MUSCLE AND EXERCISE

Adenosine transporter antagonism in humans augments vasodilator responsiveness to adenosine, but not exercise, in both adenosine responders and non-responders

Elizabeth A. Martin1, Wayne T. Nicholson1, Timothy B. Curry1, John H. Eisenach1, Nisha Charkoudian1 and Michael J. Joyner1

1 Departments of Physiology and Biomedical Engineering and Anaesthesiology, Mayo Clinic, Rochester, MN 55905, USA

' We previously demonstrated a bimodal distribution of forearm vasodilator responsiveness to adenosine (ADO) infusion in the brachial arteries of human subjects. We also demonstrated that ADO receptor antagonism blunted exercise hyperaemia during heavy rhythmic handgripping, but vasodilator responses to exogenous ADO were only blunted in ADO responders. In this study, we continued investigating the contribution of ADO to exercise hyperaemia and possible differences between responders and non-responders. We hypothesized that ADO transporter antagonism would increase vasodilatation in response to exogenous ADO in responders only, but not effect exercise-mediated vasodilation. To test this hypothesis, we compared forearm vascular conductance (FVC) during infusion of ADO to FVC during handgripping before and after infusion of dipyridamole (DIP) in 20 subjects. In ADO responders, change in FVC above baseline (ml min–1 (100 mmHg)–1) for low, medium and high doses of ADO, respectively, was 58 ± 8, 121 ± 22 and 184 ± 38, and after DIP was 192 ± 32, 238 ± 50 and 310 ± 79. For non-responders, these values were 23 ± 2, 43 ± 5 and 66 ± 9, respectively, before DIP (P < 0.01 versus responders). Contrary to our hypothesis, these values were increased by DIP in non-responders (P < 0.001) and therefore not different from responders (P > 0.20). We found that ADO transporter blockade had no effect on exercise hyperaemia in either subgroup. We conclude that there may be increased ADO transporter activity in non-responders resulting in reduced ADO-mediated vasodilatation. The failure of DIP to augment exercise hyperemia under these conditions suggests that ADO concentrations may not rise enough during rhythmic handgripping to have a major impact on these responses.

(Received 16 October 2006; accepted after revision 1 December 2006; first published online 7 December 2006)
Corresponding author E. A. Martin: Department of Anesthesiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Email: martin.elizabeth2{at}mayo.edu




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