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.
- Delta opioid receptors
- K channels
- Ventricular fibrillation threshold
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)