Cardioprotection by kappa-opioid receptor agonist U50488H is mediated by opioidergic regulation but not by calcium current modulation.
10.4097/kjae.2010.58.2.162
- Author:
Kook Jin CHUN
1
;
Young Ho JANG
;
June Hong KIM
;
Jun KIM
;
Yong Hyun PARK
Author Information
1. Institute of Cardiovascular Research Center, Pusan National University Yangsan Hospital, Yangsan, Korea. weonjo@pnuyh.co.kr
- Publication Type:Original Article
- Keywords:
Coronary occlusion;
Myocardial infarction;
Opioid receptors;
Reperfusion
- MeSH:
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
- From:Korean Journal of Anesthesiology
2010;58(2):162-168
- CountryRepublic of Korea
- Language:English
-
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.
