Korean J Anesthesiol.  2010 Feb;58(2):162-168. 10.4097/kjae.2010.58.2.162.

Cardioprotection by kappa-opioid receptor agonist U50488H is mediated by opioidergic regulation but not by calcium current modulation

• Chun KJ
• Jang YH
• Kim JH
• Kim J
• Park YH

• KMID: 2092272
• DOI: http://doi.org/10.4097/kjae.2010.58.2.162

Abstract

BACKGROUND
Because the kappa-opioid receptor (OR) agonist U50488H stimulates opioidergic regulation and inhibits L-type Ca2+ channels, this study was aimed at assessing the roles of OR and L-type Ca2+ channels on U50488H-induced cardioprotection. METHODS: Langendorff-perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Isolated hearts were treated with U50488H with or without the kappa-OR antagonist nor-binaltorphimine (nor-BNI) or the Ca2+ channels activator BAY K 8644. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining. RESULTS: U50488H treatment at reperfusion: (1) significantly reduced infarct size (11.3 +/- 1.3%) compared to control hearts (27.7 +/- 1.1%, P < 0.001), an effect that was completely blocked by nor-BNI (24.0 +/- 0.9%, P < 0.001 vs. U50488H) but not by BAY K 8644 (7.1 +/- 1.7%, P > 0.05 vs. U50488H); (2) significantly increased left ventricular developed pressure (65.3 +/- 4.8%) after 2 h of reperfusion compared to control hearts (44.8 +/- 3.6%, P < 0.05), an effect that was abrogated by nor-BNI (40.5 +/- 4.5%, P > 0.05 vs. control) but not by BAY K 8644 (64.3 +/- 5.6%, P < 0.01 vs. control); and (3) significantly decreased heart rate (P < 0.01 vs. control), an effect that was completely abrogated by both nor-BNI and BAY K 8644. CONCLUSIONS: U50488H significantly limits myocardial infarction and stunning in isolated rat hearts after ischemia-reperfusion induction. The infarct size limitation and contractility improvement observed with U50488H treatment during reperfusion are entirely mediated by OR stimulation and not by Ca2+ channel modulation.

Keyword

Coronary occlusion; Myocardial infarction; Opioid receptors; Reperfusion

MeSH Terms

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Animals
Calcium
Coronary Occlusion
Heart
Heart Rate
Ischemia
Myocardial Infarction
Naltrexone
Rats
Receptors, Opioid
Reperfusion
Tetrazolium Salts
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Calcium
Naltrexone
Receptors, Opioid
Tetrazolium Salts