Morphine-induced postconditioning modulates mitochondrial permeability transition pore opening via delta-1 opioid receptors activation in isolated rat hearts.
10.4097/kjae.2011.61.1.69
- Author:
June Hong KIM
1
;
Kook Jin CHUN
;
Yong Hyun PARK
;
Jun KIM
;
Jeong Su KIM
;
Young Ho JANG
;
Mi Young LEE
;
Jae Hong PARK
Author Information
1. Institute of Cardiovascular Research, Pusan National University Yangsan Hospital, Yangsan, Korea. weonjo@pnuyh.co.kr
- Publication Type:Original Article
- Keywords:
Mitochondrial permeability transition pore;
Morphine;
Opioid receptors;
Postconditioning;
Reperfusion injury
- MeSH:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;
Animals;
Atractyloside;
Benzylidene Compounds;
Heart;
Heart Rate;
Ischemia;
Ischemic Postconditioning;
Mitochondrial Membrane Transport Proteins;
Morphine;
Myocardial Infarction;
Naloxone;
Naltrexone;
Permeability;
Rats;
Receptors, Opioid;
Reperfusion;
Reperfusion Injury;
Tetrazolium Salts
- From:Korean Journal of Anesthesiology
2011;61(1):69-74
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post). METHODS: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 1 microM morphine, with or without the OR antagonists or a MPTP opener at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining. RESULTS: There were no significant differences in cardiodynamic variables except a decrease in heart rate in the M-Post group (P < 0.01 vs. control) after reperfusion. M-Post dramatically reduced infarct-risk volume ratio (9.8 +/- 2.5%, P < 0.001 vs. 30.0 +/- 3.7% in control). This beneficial effect on infarct volume by M-Post was comparable with ischemic postconditioning (11.9 +/- 2.2%, P > 0.05). The nonspecific OR antagonist naloxone (25.7 +/- 1.9%, P < 0.01), the delta-OR antagonist naltrindole (27.8 +/- 4.3%, P < 0.05) and delta1-OR antagonist 7-benzylidenenaltrexone (24.7 +/- 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition, the anti-infarct effect by M-Post was also totally blocked by the MPTP opener atractyloside (26.3 +/- 5.2%, P < 0.05). CONCLUSIONS: M-Post effectively reduces myocardial infarction. The anti-infarct effect by M-Post is mediated via activation of delta-OR, especially delta1-OR, and inhibition of the MPTP opening.
