Evidence for a role of opioids in epoxyeicosatrienoic acid-induced cardioprotection in rat hearts
| Autor: | Garrett J. Gross, John R. Falck, John E. Baker, Kasem Nithipatikom, Anna Hsu, Hsiang En Wu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Physiology Narcotic Antagonists Myocardial Infarction Myocardial Reperfusion Injury (+)-Naloxone GTP-Binding Protein alpha Subunits Gi-Go Pharmacology Epoxyeicosatrienoic acid Naltrexone Rats Sprague-Dawley chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid Physiology (medical) medicine Animals Myocardial infarction Receptor Cardioprotection Naloxone business.industry Articles Infarct size medicine.disease Rats Analgesics Opioid Disease Models Animal Somatostatin chemistry Receptors Opioid cardiovascular system lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 298:H2201-H2207 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | We previously demonstrated that several epoxyeicosatrienoic acids (EETs) produce reductions in myocardial infarct size in rats and dogs. Since a recent study demonstrated the release of opioids in mediating the antinociceptive effect of 14,15-EET, we hypothesized that endogenous opioids may also be involved in mediating the cardioprotective effect of the EETs. To test this hypothesis, we used an in vivo rat model of infarction and a rat Langendorff model. In the infarct model, hearts were subjected to 30 min occlusion of the left coronary artery and 2 h reperfusion. Animals were treated with 11,12-EET or 14,15-EET (2.5 mg/kg) alone 15 min before occlusion or with opioid antagonists [naloxone, naltrindole, nor-binaltorphimine (nor-BNI), and d-Phe-Cys-Tyr-d-Trp-Om-Thr-Pen-Thr-NH(2) (CTOP), a nonselective, a selective delta, a selective kappa, and a selective mu receptor antagonist, respectively] 10 min before EET administration. In four separate groups, antiserum to Met- and Leu-enkephalin and dynorphin-A-(1-17) was administered 50 min before the 11,12-EET administration. Infarct size expressed as a percent of the area at risk (IS/AAR) was 63.5 + or - 1.2, 45.3 + or - 1.0, and 40.9 + or - 1.2% for control, 11,12-EET, and 14,15-EET, respectively. The protective effects of 11,12-EET were abolished by pretreatment with either naloxone (60.5 + or - 1.8%), naltrindole (60.8 + or - 1.0%), nor-BNI (62.3 + or - 2.8%), or Met-enkephalin antiserum (63.2 + or - 1.7%) but not CTOP (42.0 + or - 3.0%). In isolated heart experiments, 11,12-EET was administered to the perfusate 15 min before 20 min global ischemia followed by 45 min reperfusion in control hearts or in those pretreated with pertussis toxin (48 h). 11,12-EET increased the recovery of left ventricular developed pressure from 33 + or - 1 to 45 + or - 6% (P0.05) and reduced IS/AAR from 37 + or - 4 to 20 + or - 3% (P0.05). Both pertussis toxin and naloxone abolished these beneficial effects of 11,12-EET. Taken together, these results suggest that the major cardioprotective effects of the EETs depend on activation of a G(i/o) protein-coupled delta- and/or kappa-opioid receptor. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|