Activation of peripheral δ opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K+ channels

L. N. Maslov, Yu B. Lishmanov, N. V. Solenkova, G. J. Gross, G. B. Stefano, S. W. Tam

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The effects of the selective delta-1 (δ1) opioid receptor agonist, DPDPE, and the selective δ2 opioid receptor agonist, DSLET, have been studied on the ventricular fibrillation threshold (VFT) in rats with an experimental post-infarction cardiosclerosis (CS). It has been found that CS induced a significant decrease in VFT. This CS-induced decrease in VFT was significantly reversed by intravenous administration of DPDPE (0.1 mg/kg) 10 min before VFT measurement. On the contrary, intravenous injection of DSLET (0.5 mg/kg) exacerbated the CS-induced cardiac electrical instability. Pretreatment with the selective δ opioid receptor antagonist, ICI 174,864 (0.5 mg/kg), completely abolished the changes in VFT produced by both DPDPE and DSLET. Previous administration of a nonselective peripherally acting opioid receptor antagonist, naloxone methiodide (5 mg/kg) also completely reversed the antifibrillatory action of DPDPE. Naloxone methiodide and ICI 174,864 alone had no effect on VFT. Pretreatment with the nonselective KATP channel blocker, glibenclamide (0.3 mg/kg), or with the mitochondrial selective KATP channel blocker, 5-hydroxydecanoic acid (5-HD, 5 mg/kg), completely abolished the DPDPE-induced increase in cardiac electrical stability. Glibenclamide and 5-HD alone had no effect on VFT. These results demonstrate that the δ opioid receptor plays an important role in the regulation of electrical stability in rats with post-infarction cardiosclerosis. We propose that peripheral δ1 opioid receptor stimulation reverses CS-induced electrical instability via mitochondrial KATP channels. On the contrary, δ2 opioid receptor stimulation may exacerbate the CS-induced decrease in VFT. Further studies are necessary to determine the δ opioid receptor subtype which mediates the antifibrillatory effect of DPDPE and pro-fibrillatory effect of DSLET.

Original languageEnglish
Pages (from-to)947-952
Number of pages6
JournalLife Sciences
Volume73
Issue number7
DOIs
Publication statusPublished - 4 Jul 2003

Keywords

  • Cardiosclerosis
  • Delta opioid receptors
  • K channels
  • Rat
  • Ventricular fibrillation threshold

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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