Ischemic Postconditioning Inhibits Mitochondrial Permeability Transition Pore via Opioid Receptor Activation in Intact Rat Heart.
10.4097/kjae.2008.54.3.320
- Author:
Yong Cheol LEE
1
;
Young Ho JANG
;
Jin Mo KIM
;
Ae Ra KIM
;
Seung Ryong LEE
;
Yoon Nyun KIM
;
Ji Hee HONG
Author Information
1. Department of Anesthesiology and Pain Medicine, School of Medicine, Keimyung University, Daegu, Korea. eonjo@hotmail.com
- Publication Type:Original Article
- Keywords:
ischemia;
mitochondria;
opioid receptor;
postconditioning;
reperfusion
- MeSH:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;
Animals;
Atractyloside;
Coronary Vessels;
Glycogen Synthase Kinase 3;
Glycogen Synthase Kinases;
Heart;
Humans;
Indoles;
Ischemia;
Ischemic Postconditioning;
Male;
Maleimides;
Mitochondria;
Mitochondrial Membrane Transport Proteins;
Myocardial Ischemia;
Myocardium;
Naloxone;
Naltrexone;
Permeability;
Rats;
Rats, Wistar;
Receptors, Opioid;
Reperfusion
- From:Korean Journal of Anesthesiology
2008;54(3):320-327
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Ischemic postconditioning (Post-C), brief cycles of myocardial ischemia and reperfusion during the early phase of reperfusion, is considered as a novel adjunct strategy to protect myocardium.However, the exact mechanism remains unclear and should be determined. METHODS: The hearts of male Wistar rats were subjected to 30 min ischemia and 2 hrs reperfusion.Control rats had no intervention either before or after left coronary artery occlusion.Post-C was elicited by 6 cycles of 10s reperfusioninterspersed by 10s ischemia immediately after onset of reperfusion.Subsets of postconditioning rats were treated with drugs as followings; naloxone (non-selective opioid receptor antagonist), naltrindole (a delta-opioid receptor antagonist), SB216763 (a glycogen synthase kinase 3beta inhibitor, GSK-3beta inhibitor), or atractyloside (a mitochondrial permeability transition pore opener, mPTP opener). RESULTS: Post-C significantly reduced infarct size (15.9 +/- 2.4%, P = 0.003) compared to control (29.9 +/- 3.7%).The anti-infarct effect by Post-C was blocked by both naloxone (25.5 +/- 3.9%, P = 0.044) and naltrindole (26.9 +/- 2.3%, P = 0.022).Infarct size limiting effect by Post-C was also abolished by atractyloside (30.6 +/- 3.6%, P = 0.003).In SB216763 with naloxone treated animals, the infarct size was decreased (17.4 +/- 3.2%, P = 0.007) but not in SB216763 with atractyloside treated animals (27.4 +/- 2.6%) compared to control. CONCLUSIONS: These data suggest that Post-C may protect myocardium by inhibiting mPTP opening via delta-opioid receptor activation.GSK-3beta is a downstream mediator of opioid receptors and an upstream mediator of mPTP opening in Post-C.
