Opioid-induced cardioprotection against myocardial infarction and arrhythmias: mitochondrial versus sarcolemmal ATP-sensitive potassium channels. J Pharmacol Exp Ther 2000 Aug;294(2):451-7
Date
07/20/2000Pubmed ID
10900218Scopus ID
2-s2.0-0033913629 (requires institutional sign-in at Scopus site) 132 CitationsAbstract
We examined the role of the sarcolemmal and mitochondrial ATP-sensitive potassium (K(ATP)) channel in a rat model of myocardial infarction after stimulation with the selective delta(1)-opioid receptor agonist TAN-67. Hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Infarct size was expressed as a percentage of the area at risk. TAN-67 significantly reduced infarct size/area at risk (29.6 +/- 3.3) versus control (63. 1 +/- 2.3). The sarcolemmal-selective K(ATP) channel antagonist HMR 1098, administered 10 min before TAN-67, did not significantly attenuate cardioprotection (26.0 +/- 7.3) at a dose (3 mg/kg) that had no effect in the absence of TAN-67 (56.3 +/- 4.3). Pretreatment with the mitochondrial selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before the 30-min occlusion completely abolished TAN-67-induced cardioprotection (54.3 +/- 2.7), but had no effect in the absence of TAN-67 (62.6 +/- 4.1), suggesting the involvement of the mitochondrial K(ATP) channel. Additionally, we examined the antiarrhythmic effects of TAN-67 in the presence or absence of 5-HD and HMR 1098 during 30 min of ischemia. Control animals had an average arrhythmia score of 10.40 +/- 2.41. TAN-67 significantly reduced the arrhythmia score during 30 min of ischemia (2.38 +/- 0. 85). 5-HD and HMR 1098 in the absence of TAN-67 produced an insignificant decrease in the arrhythmia score (8.80 +/- 2.56 and 4. 20 +/- 1.07, respectively). 5-HD administration before TAN-67 treatment abolished its antiarrhythmic effect (4.71 +/- 1.11). However, HMR 1098 did not abolish TAN-67-induced protection against arrhythmias (1.67 +/- 0.80). These data suggest that delta(1)-opioid receptor stimulation is cardioprotective against myocardial ischemia and sublethal arrhythmias and suggest a role for the mitochondrial K(ATP) channel in mediating these cardioprotective effects.
Author List
Fryer RM, Hsu AK, Nagase H, Gross GJMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnalgesics, Opioid
Animals
Anti-Arrhythmia Agents
Arrhythmias, Cardiac
Benzamides
Blood Pressure
Decanoic Acids
Drug Interactions
Heart Rate
Hydroxy Acids
Male
Mitochondria, Heart
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Potassium Channel Blockers
Potassium Channels
Quinolines
Rats
Rats, Wistar
Receptors, Opioid, delta
Sarcolemma
Ventricular Fibrillation
