Activation of peripheral delta opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K+ channels. Life Sci 2003 Jul 04;73(7):947-52
Date
06/12/2003Pubmed ID
12798419DOI
10.1016/s0024-3205(03)00348-5Scopus ID
2-s2.0-0037836012 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
The effects of the selective delta-1 (delta(1)) opioid receptor agonist, DPDPE, and the selective delta(2) 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 delta 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 K(ATP) channel blocker, glibenclamide (0.3 mg/kg), or with the mitochondrial selective K(ATP) 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 delta opioid receptor plays an important role in the regulation of electrical stability in rats with post-infarction cardiosclerosis. We propose that peripheral delta(1) opioid receptor stimulation reverses CS-induced electrical instability via mitochondrial K(ATP) channels. On the contrary, delta(2) opioid receptor stimulation may exacerbate the CS-induced decrease in VFT. Further studies are necessary to determine the delta opioid receptor subtype which mediates the antifibrillatory effect of DPDPE and pro-fibrillatory effect of DSLET.
Author List
Maslov LN, Lishmanov YB, Solenkova NV, Gross GJ, Stefano GB, Tam SWMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnalgesics, Opioid
Animals
Decanoic Acids
Disease Models, Animal
Drug Antagonism
Enkephalin, D-Penicillamine (2,5)-
Enkephalin, Leucine
Glyburide
Hydroxy Acids
Male
Mitochondria, Heart
Myocardial Infarction
Myocardium
Naloxone
Potassium Channels
Quaternary Ammonium Compounds
Rats
Rats, Wistar
Receptors, Opioid, delta
Sclerosis
Ventricular Fibrillation
