Premium
Comparative analysis of cardioprotective and antiarrhythmic properties of opioid receptor agonists in a rat model of myocardial infarction
Author(s) -
Brown Stephen A.,
Maslov Leonid N.,
Oeltgen Peter R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.793.9
Subject(s) - (+) naloxone , antagonist , pharmacology , chemistry , opioid antagonist , naltrexone , opioid receptor , verapamil , enkephalin , medicine , agonist , atenolol , opioid peptide , opioid , endocrinology , receptor , blood pressure , calcium
We examined the effect of opioid receptor (OR) agonists/antagonists and inhibitors on infarct size (IS) and arrhythmia in rats following coronary artery occlusion and reperfusion. Pretreatment with the specific δ 2 ‐OR agonist Deltorphin II reduced the IS and was prevented by treatment with naltrexone, naloxone and the specific δ 2 ‐OR antagonist naltriben (NTB). The infarct‐limiting effect of Deltorphin II was also abolished by inhibition of Protein Kinase C (PKC) and potassium ATP‐sensitive K (K ATP ) channels but not by the specific δ 1 ‐OR antagonist, 7‐Benzylidennaltrexone (BNTX). All deltorphins tested exhibited antiarrhythmic properties during phase 1b of ischemia, but only Deltorphin II prevented ventricular arrhythmias during phase 1a and phase 1b. The antiarrhythmic effect of deltorphin II was abolished by treatment with naltrexone, naloxone methiodide and the selective δ 2 ‐OR antagonist NTB but not by the selective δ 1 ‐OR antagonist BNTX. PKC inhibition, but not K ATP channel inhibition, eliminated the antiarrhythmic effect of Deltorphin II. Pretreatment with other opioids D‐Ala 2 , N‐Me‐Phe 4 , Gly 5 ‐ol‐Enkephalin, Dermorphin H, D‐Pen 2,5 Enkephalin, Deltorphin‐D, Deltorphin‐E, and U‐50,488, nociception did not reduce the IS or arrhythmias. We conclude that peripheral δ 2 ‐OR activation induces infarct size reduction and prevents ischemia induced ventricular arrhythmias.