title: Adenosine transporter antagonism in humans augments vasodilator responsiveness to adenosine, but not exercise, in both adenosine responders and non-responders.
abstract: ' 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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. martin.elizabeth2@mayo.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Martin
authors.forename: Wayne T
authors.initials: WT
authors.lastname: Nicholson
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Curry
authors.forename: John H
authors.initials: JH
authors.lastname: Eisenach
authors.forename: Nisha
authors.initials: N
authors.lastname: Charkoudian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D004176:Dipyridamole / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D033703:Nucleoside Transport Proteins; D014665:Vasodilator Agents; C444719:adenosine transporter; D004176:Dipyridamole; D000241:Adenosine