Contribution of Adenosine A_2A and A_2B Receptors to Ischemic Coronary Dilation: Role of K_V and K_ATP Channels

This study was designed to elucidate the contribution of adenosine A_2A and A_2B 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 A_2A receptors with SCH58261 (1 μm) attenuated adenosine-induced dilation by ~50%, while combined administration with the A_2B 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. A_2A 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 K_V channels with 4-aminopyridine (0.3 mm) and to 0.11 ± 0.31 mL/minute/g by inhibition of K_ATP channels with glibenclamide (3 mg/kg). Combined administration abolished vasodilation to CGS21680. These data indicate that A_2A receptors contribute to coronary vasodilation in response to cardiac ischemia via activation of K_V and K_ATP channels.