Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs.
The objective of the present study was to characterize the role of adenosine in myocardial ischemic preconditioning in the canine heart. Preconditioning with 5 min of ischemia resulted in a marked reduction in infarct size after 60 min of left circumflex coronary artery occlusion and 5 h of reperfusion in barbital-anesthetized dogs compared with dogs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.05). Pretreatment with either the nonselective adenosine receptor antagonist PD 115199 or the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked this protective effect, although in the absence of preconditioning neither of the antagonists affected infarct size. Intracoronary infusion of two different doses of adenosine or dipyridamole over a 5-min period before a prolonged 60-min occlusion period did not mimic preconditioning; however, intracoronary infusion of a combination of adenosine and dipyridamole produced a significant reduction in infarct size (13.6 +/- 4.1%), which was abolished by pretreatment with the ATP-dependent potassium (KATP) channel antagonist glibenclamide. These results suggest that activation of adenosine A1 receptors produces myocardial preconditioning in the canine heart by opening KATP channels.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
J A
JA
Auchampach
G J
GJ
Gross
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015425:Myocardial Reperfusion; D015221:Potassium Channels / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000241:Adenosine; D000255:Adenosine Triphosphate; D001786:Blood Glucose; D005905:Glyburide; D015221:Potassium Channels; D011687:Purines; D011983:Receptors, Purinergic; D013449:Sulfonamides; D014970:Xanthines; C052023:N-(2-(dimethylamino)ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C051360:1,3-dipropyl-8-cyclopentylxanthine