Contribution of Adenosine A2A and A2B Receptors to Ischemic Coronary Dilation: Role of KV and KATP Channels

Zachary C. Berwick, Gregory A. Payne, Brandon Lynch, Gregory M. Dick, Michael Sturek, Johnathan D. Tune

Research output: Contribution to journalArticle

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Abstract

This study was designed to elucidate the contribution of adenosine A2A and A2B 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 A2A receptors with SCH58261 (1 μm) attenuated adenosine-induced dilation by ~50%, while combined administration with the A2B 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. A2A 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 KV channels with 4-aminopyridine (0.3 mm) and to 0.11 ± 0.31 mL/minute/g by inhibition of KATP channels with glibenclamide (3 mg/kg). Combined administration abolished vasodilation to CGS21680. These data indicate that A2A receptors contribute to coronary vasodilation in response to cardiac ischemia via activation of KV and KATP channels.

Original languageEnglish (US)
Pages (from-to)600-607
Number of pages8
JournalMicrocirculation
Volume17
Issue number8
DOIs
StatePublished - Nov 1 2010

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Keywords

  • Adenosine receptor
  • Canine
  • Coronary vasodilation
  • Potassium channel
  • Reactive hyperemia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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