title: Delta opioid receptors: the link between exercise and cardioprotection.
abstract: This study investigated the role of opioid receptor (OR) subtypes as a mechanism by which endurance exercise promotes cardioprotection against myocardial ischemia-reperfusion (IR) injury. Wistar rats were randomly divided into one of seven experimental groups: 1) control; 2) exercise-trained; 3) exercise-trained plus a non-selective OR antagonist; 4) control sham; 5) exercise-trained plus a kappa OR antagonist; 6) exercise-trained plus a delta OR antagonist; and 7) exercise-trained plus a mu OR antagonist. The exercised animals underwent 4 consecutive days of treadmill training (60 min/day at ∼70% of maximal oxygen consumption). All groups except the sham group were exposed to an in vivo myocardial IR insult, and the myocardial infarct size (IS) was determined histologically. Myocardial capillary density, OR subtype expression, heat shock protein 72 (HSP72) expression, and antioxidant enzyme activity were measured in the hearts of both the exercised and control groups. Exercise training significantly reduced the myocardial IS by approximately 34%. Pharmacological blockade of the kappa or mu OR subtypes did not blunt exercise-induced cardioprotection against IR-mediated infarction, whereas treatment of animals with a non-selective OR antagonist or a delta OR antagonist abolished exercise-induced cardioprotection. Exercise training enhanced the activities of myocardial superoxide dismutase (SOD) and catalase but did not increase the left ventricular capillary density or the mRNA levels of HSP72, SOD, and catalase. In addition, exercise significantly reduced the protein expression of kappa and delta ORs in the heart by 44% and 37%, respectively. Together, these results indicate that ORs contribute to the cardioprotection conferred by endurance exercise, with the delta OR subtype playing a key role in this response.
authors.affiliation: Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana P
authors.initials: JP
authors.lastname: Borges
authors.affiliation: Federal University of Rio de Janeiro, Macaé, RJ, Brazil.
authors.forename: Karine S
authors.initials: KS
authors.lastname: Verdoorn
authors.affiliation: Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Anissa
authors.initials: A
authors.lastname: Daliry
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United States of America.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
authors.affiliation: Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Ortenzi
authors.affiliation: Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Fortunato
authors.affiliation: Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tibiriçá
authors.affiliation: Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcos Adriano
authors.initials: MA
authors.lastname: Lessa
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D005080:Exercise Test / Q000379:methods*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D050884:HSP72 Heat-Shock Proteins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole