Abstract
This study was designed to elucidate the contribution of adenosine A2A and A2B receptors to coronary reactive hyperemia and downstream K+ channels involved. Coronary blood flow was measured in open-chest anesthetized dogs. Adenosine dose-dependently increased coronary flow from 0.72 ± 0.1 to 2.6 ± 0.5 mL/minute/g under control conditions. Inhibition of A2A receptors with SCH58261 (1 μm) attenuated adenosine-induced dilation by ~50%, while combined administration with the A2B receptor antagonist alloxazine (3 μm) produced no additional effect. SCH58261 significantly reduced reactive hyperemia in response to a transient 15 second occlusion; debt/repayment ratio decreased from 343 ± 63 to 232 ± 44%. Alloxazine alone attenuated adenosine-induced increases in coronary blood flow by ~30% but failed to alter reactive hyperemia. A2A receptor agonist CGS21680 (10 μg bolus) increased coronary blood flow by 3.08 ± 0.31 mL/minute/g. This dilator response was attenuated to 0.76 ± 0.14 mL/minute/g by inhibition of KV channels with 4-aminopyridine (0.3 mm) and to 0.11 ± 0.31 mL/minute/g by inhibition of KATP channels with glibenclamide (3 mg/kg). Combined administration abolished vasodilation to CGS21680. These data indicate that A2A receptors contribute to coronary vasodilation in response to cardiac ischemia via activation of KV and KATP channels.
Original language | English |
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Pages (from-to) | 600-607 |
Number of pages | 8 |
Journal | Microcirculation |
Volume | 17 |
Issue number | 8 |
DOIs | |
State | Published - Nov 2010 |
Keywords
- Adenosine receptor
- Canine
- Coronary vasodilation
- Potassium channel
- Reactive hyperemia