Faculty Collaboration Database

Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs. Circ Res 1993 Dec;73(6):1193-201

Date

12/01/1993

Pubmed ID

8222090

DOI

10.1161/01.res.73.6.1193

Scopus ID

2-s2.0-0027372247 (requires institutional sign-in at Scopus site)   141 Citations

Abstract

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)

Author List

Yao Z, Gross GJ

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Adenosine Triphosphate
Animals
Coronary Circulation
Dogs
Female
Hemodynamics
Male
Myocardial Infarction
Myocardial Ischemia
Myocardium
Nitric Oxide
Potassium Channels
Receptors, Muscarinic
Risk Factors
Ventricular Fibrillation