Korean Journal of Anesthesiology (Feb 2010)

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

  • Kook Jin Chun,
  • Young Ho Jang,
  • June Hong Kim,
  • Jun Kim,
  • Yong Hyun Park

DOI
https://doi.org/10.4097/kjae.2010.58.2.162
Journal volume & issue
Vol. 58, no. 2
pp. 162 – 168

Abstract

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BackgroundBecause the κ-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.MethodsLangendorff-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 κ-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.ResultsU50488H treatment at reperfusion: (1) significantly reduced infarct size (11.3 ± 1.3%) compared to control hearts (27.7 ± 1.1%, 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 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.ConclusionsU50488H 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.

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