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Contribution of Adenosine A 2A and A 2B Receptor Subtypes to Coronary Reactive Hyperemia: Role of K V and K ATP Channels
Author(s) -
Berwick Zachary Christopher,
Lynch Brandon,
Payne Gregory,
Dick Gregory,
Sturek Michael,
Tune Johnathan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1034.8
Subject(s) - adenosine , reactive hyperemia , chemistry , medicine , adenosine receptor , cgs 21680 , coronary occlusion , vasodilation , agonist , receptor , cardiology , anesthesia , endocrinology , occlusion
This study examined the relative contribution of adenosine A 2A and A 2B receptors to coronary reactive hyperemia and the downstream K + channels involved. Coronary blood flow was measured in open‐chest anesthetized dogs via cannulation of the left anterior descending coronary artery. Adenosine (1–30 μg/min, ic) increased coronary blood flow from 0.72 ± 0.10 ml/min/g to 2.6 ± 0.50 ml/min/g under control conditions. Inhibition of A 2A or A 2B receptors with SCH58261 (1 μM, ic) and/or alloxazine (3 μM, ic) attenuated adenosine‐induced dilation by ~ 80% and 35% respectively; combined administration produced no additive effect. A 2A receptor blockade significantly reduced coronary reactive hyperemia in response to a transient 15 sec occlusion. In particular, SCH58261 diminished the debt/repayment ratio from 343 ± 63% to 232 ± 44%. Coronary reactive hyperemia was unaffected by A 2B receptor blockade. The increase in coronary flow to 3.08 ± 0.31 ml/min/g in response to the A 2A receptor agonist CGS 21680 (10 μg bolus, ic) was attenuated to 0.76 ± 0.14 ml/min/g by inhibition of voltage‐dependent K + (K v ) channels with 4‐aminopyridine (0.3 mM, ic) and to 0.11 ± 0.31 ml/min/g by inhibition of ATP‐sensitive K + (K ATP ) channels with glibenclamide (3 mg/kg, iv). These findings indicate that adenosine A 2A receptors contribute to ischemic coronary vasodilation via activation of K V and K ATP channels. Support HL092245, HL062552