Document Detail

Modulation of the cardioprotective effect of ischemic preconditioning in hyperlipidaemic rat heart.
MedLine Citation:
PMID:  20598682     Owner:  NLM     Status:  MEDLINE    
Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of cardioprotective effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks. Isolated perfused rat heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. IPC significantly decreased the myocardial infarct size and the release of LDH and CK-MB from normal rat heart. IPC induced myocardial protection was attenuated in hyperlipidaemic rat heart. However, cardioprotective effect of pharmacological preconditioning with GSK-3beta inhibitors i.e. Lithium Chloride (LiCl) (20mM), Indirubin - 3 Monooxime (1 microM) and 3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione (SB216763) (3 microM), was not attenuated. This differential attenuation by hyperlipidaemia, of IPC and pharmacological preconditioning induced cardioprotection is a new finding in our study. GSK-3beta inhibition is reported to increase the threshold of opening for MPTP during reperfusion. Administration of atractyloside (20 microM), an opener of MPTP, significantly attenuated the cardioprotective effect of IPC in normal heart, and pharmacological preconditioning in the hyperlipidaemic rat heart. Thus, the attenuation of cardioprotective effect of IPC in hyperlipidaemic heart may be due to inhibition of protective signaling pathways upstream of GSK-3beta and inhibition of opening of MPTP.
Harlokesh Narayan Yadav; Manjeet Singh; Pyare Lal Sharma
Publication Detail:
Type:  Journal Article     Date:  2010-06-20
Journal Detail:
Title:  European journal of pharmacology     Volume:  643     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-12-07     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  78-83     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Department of Pharmacology, I.S.F. College of Pharmacy, Moga-142001, Punjab, India.
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MeSH Terms
Dietary Fats
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors,  metabolism
Hyperlipidemias / complications*,  enzymology,  metabolism
Ischemic Preconditioning, Myocardial*
Mitochondrial Membrane Transport Proteins / antagonists & inhibitors
Myocardial Infarction / complications,  enzymology,  metabolism,  prevention & control*
Myocardial Reperfusion Injury / complications,  enzymology,  metabolism,  prevention & control*
Rats, Wistar
Reg. No./Substance:
0/Dietary Fats; 0/Enzyme Inhibitors; 0/Mitochondrial Membrane Transport Proteins; 0/mitochondrial permeability transition pore; EC synthase kinase 3 beta; EC Synthase Kinase 3

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