Premium
Contribution of Adenosine A 2A and A 2B Receptors to Ischemic Coronary Dilation: Role of K V and K ATP Channels
Author(s) -
BERWICK ZACHARY C,
PAYNE GREGORY A,
LYNCH BRANDON,
DICK GREGORY M,
STUREK MICHAEL,
TUNE JOHNATHAN D.
Publication year - 2010
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2010.00054.x
Subject(s) - adenosine , adenosine receptor , vasodilation , reactive hyperemia , medicine , dilator , nicorandil , adenosine a2a receptor , cardiology , adenosine receptor antagonist , coronary occlusion , agonist , coronary circulation , anesthesia , blood flow , receptor , chemistry , ischemia
Please cite this paper as: Berwick, Payne, Lynch, Dick, Sturek and Tune (2010). Contribution of Adenosine A 2A and A 2B Receptors to Ischemic Coronary Dilation: Role of K V and K ATP Channels. Microcirculation 17(8) , 600–607. 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 μ m ) attenuated adenosine‐induced dilation by ∼50%, while combined administration with the A 2B receptor antagonist alloxazine (3 μ 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 ∼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 m m ) 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.