Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs.
The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Preconditioning was elicited by 10 minutes of LAD occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. ACh (3 or 10 micrograms/min) or an equivalent volume of saline was infused into the LAD for 10 minutes, followed by a 10-minute drug-free period before the 60-minute ischemic insult. In other groups, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA, 4 mg/min), the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 3 mg/min), or the specific KATP channel blocker 5-hydroxydecanoate (5-HD, 3 mg/min) was infused with ACh into the LAD for 10 minutes. The infusion of L-NAME, L-NMMA, or 5-HD was started 2 minutes before ACh infusion. Transmural myocardial blood flow was measured at 5 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percentage of the area at risk. There were no significant differences in collateral blood flow or the area at risk between groups. Preconditioning produced a marked reduction (P < .05) in infarct size (6.2 +/- 3.0% versus 26.1 +/- 5.7% in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)
Yao
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Gross
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D000109:Acetylcholine; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012307:Risk Factors; D014693:Ventricular Fibrillation / Q000139:chemically induced
D015221:Potassium Channels; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000109:Acetylcholine