The effects of κ-opioid receptor on stretch-induced electrophysiological changes in infarcted rat hearts

Am J Med Sci. 2013 Feb;345(2):129-35. doi: 10.1097/MAJ.0b013e31824ceba7.

Abstract

Introduction: Kappa-opioid receptors (κ-OR) and mechanoelectric feedback seem to have common pathways that influence electrophysiological changes resulting from acute myocardial infarction (MI). This study aims to determine the effects of the κ-OR on stretch-induced electrophysiological changes after acute MI.

Methods: Male Sprague-Dawley rats were randomly divided into 4 groups: sham operated, MI, U-50488H (a selective κ-OR agonist) -treated MI (MI+U-50488H) and nor-BNI (a selective κ-OR antagonist) -treated MI (MI+nor-BNI). After Langendorff perfusion to maintain stabilization, a transient stretch (5 seconds) was delivered early in diastole. Electrophysiological changes were recorded for 1 minute before and after stretch. Similarly, the 20%, 50% and 90% monophasic action potential duration (MAPD20, MAPD50 and MAPD90, respectively) and stretch-induced arrhythmias were recorded.

Results: MAPD90 significantly increased in all 4 groups. MAPD90 in the MI and MI+nor-BNI groups increased significantly before stretch (P < 0.05) and after stretch (P < 0.01) but was reversed in the MI+U-50488H group (P > 0.05). MAPD90 in the MI group was increased compared with that of the MI+U-50488H group but decreased compared with that of the MI+ nor-BNI group after stretch (P < 0.01). The arrhythmia score in the MI and MI+nor-BNI groups was higher than that of the sham-operated group (P < 0.01), and the arrhythmia score in the MI+nor-BNI group was higher than that in MI group after stretch (P < 0.01). The arrhythmia score of the MI+U-50488H group was lower than that of MI group after stretch (P < 0.01).

Conclusions: The κ-OR could influence the stretch-induced electrophysiological changes and play an antiarrhythmic role in stretch-induced arrhythmias after acute MI.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Arrhythmias, Cardiac / physiopathology
  • Electrophysiological Phenomena / drug effects
  • Electrophysiological Phenomena / physiology
  • Male
  • Myocardial Infarction / physiopathology*
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Pressoreceptors / drug effects
  • Pressoreceptors / physiology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / physiology*

Substances

  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer