Contribution of Adenosine A2A and A2B Receptors to Ischemic Coronary Dilation: Role of KV and KATP 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 mu m) attenuated adenosine-induced dilation by similar to 50%, while combined administration with the A(2B) receptor antagonist alloxazine (3 mu m) 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 similar to 30% but failed to alter reactive hyperemia. A(2A) receptor agonist CGS21680 (10 mu g 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.