Cardioprotection by kappa-opioid receptor agonist U50488H is mediated by opioidergic regulation but not by calcium current modulation.
BACKGROUND
Because the kappa-opioid receptor (OR) agonist U50488H stimulates opioidergic regulation and inhibits L-type Ca(2+) channels, this study was aimed at assessing the roles of OR and L-type Ca(2+) 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 Ca(2+) 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 Ca(2+) channel modulation.
Chun
Kook Jin
KJ
Institute of Cardiovascular Research Center, Pusan National University Yangsan Hospital, Yangsan, Korea.
Jang
Young Ho
YH
Kim
June Hong
JH
Kim
Jun
J
Park
Yong Hyun
YH