Faculty Collaboration Database

Opioid-induced second window of cardioprotection: potential role of mitochondrial KATP channels. Circ Res 1999 Apr 16;84(7):846-51

Date

04/16/1999

Pubmed ID

10205153

DOI

10.1161/01.res.84.7.846

Scopus ID

2-s2.0-0033574686 (requires institutional sign-in at Scopus site)   207 Citations

Abstract

Opioids have been previously shown to confer short-term cardioprotection against a prolonged ischemic insult. Therefore, the present study was designed to determine whether opioids can induce a delayed or "second window" of cardioprotection and to assess the potential involvement of the mitochondrial KATP channel. All rats were subjected to 30 minutes of ischemia and 2 hours of reperfusion (I/R). Control animals, injected with saline 24 hours before I/R, elicited an infarct size/area at risk (IS/AAR) of 62.9+/-3.4. TAN-67, a delta1-opioid receptor agonist, was administered 10 or 30 mg/kg IP 12, 24, 48, or 72 hours before I/R. TAN-67 (10 mg/kg) 12- or 24-hour pretreatment did not significantly reduce IS/AAR (62.1+/-6.3 and 43.3+/-7.3, respectively). Similarly, 12-hour pretreatment with TAN-67 (30 mg/kg) did not reduce IS/AAR (60.0+/-5.6); however, 24-hour pretreatment significantly reduced IS/AAR (34.5+/-5.9). Forty-eight-hour pretreatment with TAN-67 maximally reduced IS/AAR (29.2+/-7.0), and opioid-induced cardioprotection was lost after 72-hour pretreatment (61.7+/-3.8). TAN-67-induced cardioprotection could be abolished by pretreatment with the selective delta1-opioid receptor antagonist 7-benzylidenenaltrexone, BNTX, administered either 30 minutes before TAN-67 given 48 hours before I/R or 10 minutes before I/R in rats previously treated for 48 hours with TAN-67 (59.6+/-3.1 and 58.7+/-3.5, respectively). The involvement of the KATP channel was investigated with 2 inhibitors: glibenclamide, a nonselective KATP channel inhibitor, and 5-hydroxydecanoic acid, selective for the mitochondrial KATP channel in rabbits. Glibenclamide, administered 30 minutes before I/R in 48-hour TAN-67-pretreated rats, completely abolished cardioprotection (60. 4+/-3.2). Similarly, 5-hydroxydecanoic acid, administered 5 minutes before I/R in rats pretreated 48 hours previously with TAN-67, completely abolished cardioprotection (57.8+/-2.5). These results suggest that delta1-opioid receptor stimulation, 24 to 48 hours before an ischemic insult, produces a delayed cardioprotective effect that is possibly the result of mitochondrial KATP channel activation.

Author List

Fryer RM, Hsu AK, Eells JT, Nagase H, Gross GJ

Author

Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Analgesics
Animals
Benzylidene Compounds
Blood Pressure
Coronary Circulation
Glyburide
Hypoglycemic Agents
Ischemic Preconditioning, Myocardial
Male
Mitochondria
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Myocardium
Naltrexone
Narcotic Antagonists
Potassium Channels
Quinolines
Rats
Rats, Wistar
Receptors, Opioid, delta