Contribution of adenosine A(2A) and A(2B) receptors to ischemic coronary dilation: role of K(V) and K(ATP) 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 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.
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Zachary C
ZC
Berwick
Gregory A
GA
Payne
Brandon
B
Lynch
Gregory M
GM
Dick
Michael
M
Sturek
Johnathan D
JD
Tune
D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005415:Flavins / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010627:Phenethylamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D005415:Flavins; D054086:KATP Channels; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C008173:isoalloxazine; D015761:4-Aminopyridine; D000241:Adenosine; D005905:Glyburide