Ligands for opioid and σ-receptors improve cardiac electrical stability in rat models of post-infarction cardiosclerosis and stress

Yu B. Lishmanov, L. N. Maslov, N. V. Naryzhnaya, S. W. Tam

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25 Citations (Scopus)

Abstract

The effects of the extremely selective μ-opioid receptor agonist, [D- Arg2,Lys4]dermorphin-(1-4)-amide (DALDA), the μ-opioid receptor agonist morphine, the μ/δ agonist D-Ala2, Leu5, Arg6-enkephalin (dalargin), the κ-opioid receptor agonist spiradoline, and the σ1-receptor antagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigated in an experimental post-infarction cardiosclerosis model and an immobilization stress-induced model in rats. Both models produced a significant decrease in VFT. The postinfarction cardiosclerosis-induced decrease in VFr was significantly reversed by intravenous administration of dalargin (0.1 mg/kg), DALDA (0.1 mg/kg), or morphine HCl (1.5 mg/kg). Pretreatment with naloxone (0.2 mg/kg) completely eliminated the increase in cardiac electrical stability produced by DALDA. Both spiradoline (8 mg/kg, i.p.) and DuP 734 (1 mg/kg, i.p.) produced a significant increase in VFT in rats with postinfarction cardiosclerosis. This effect of spiradoline was blocked by nor-binaltorphimine. The immobilization stress-induced decrease in VFT was significantly reversed by administration of either DALDA, spiradoline or DuP 734. In conclusion, activation of either μ- or κ1-opioid receptors or blockade of σ1-receptors reversed the decrease in VFT in both cardiac compromised models. Since DALDA and dalargin essentially do not cross blood brain barriers, their effects on VFT may be mediated through peripheral μ- opioid receptors.

Original languageEnglish
JournalLife Sciences
Volume65
Issue number1
DOIs
Publication statusPublished - 28 May 1999

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Keywords

  • Cardiac arrhythmias
  • Cardiosclerosis
  • Opioid receptors
  • Rat
  • Sigma receptor
  • Stress

ASJC Scopus subject areas

  • Pharmacology

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