Delta opioid receptors: the link between exercise and cardioprotection

• Published in: PloS one Vol. 9; no. 11; p. e113541
• Main Authors: Borges, Juliana P, Verdoorn, Karine S, Daliry, Anissa, Powers, Scott K, Ortenzi, Victor H, Fortunato, Rodrigo S, Tibiriçá, Eduardo, Lessa, Marcos Adriano
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21-11-2014; Public Library of Science (PLoS)
• Subjects: Animals; Antioxidants; Antioxidants (Nutrients); Biology and Life Sciences; Biophysics; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Catalase; Disease Models, Animal; Enzymatic activity; Enzyme activity; Enzymes; Exercise; Exercise Test - methods; Experiments; Heart; Heart - drug effects; Heart attacks; Heat shock; Heat shock proteins; HSP72 Heat-Shock Proteins - metabolism; Hsp72 protein; In vivo methods and tests; Infarction; Ischemia; Laboratory animals; Male; Medicine and Health Sciences; mRNA; Myocardial infarction; Myocardial ischemia; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Naltrexone - administration & dosage; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - pharmacology; Narcotics; NMR; Nuclear magnetic resonance; Opioid receptors (type delta); Oxygen; Oxygen consumption; Pharmacology; Rats; Rats, Wistar; Receptors; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, delta - metabolism; Reperfusion; RNA; Rodents; Studies; Superoxide dismutase; Superoxides; Training; Ventricle; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113541

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.