Contribution of adenosine A(2A) and A(2B) receptors to ischemic coronary dilation: role of K(V) and K(ATP) channels.

Abstract

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 (0.3mm) 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.