Document Detail


Lovastatin interferes with the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts.
MedLine Citation:
PMID:  18359895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Statins have been shown to be cardioprotective; however, their interaction with endogenous cardioprotection by ischemic preconditioning and postconditioning is not known. In the present study, we examined if acute and chronic administration of the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor lovastatin affected the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. Wistar rats were randomly assigned to the following three groups: 1) vehicle (1% methylcellulose per os for 12 days), 2) chronic lovastatin (15 mg.kg(-1).day(-1) per os for 12 days), and 3) acute lovastatin (1% methylcellulose per os for 12 days and 50 micromol/l lovastatin in the perfusate). Hearts isolated from the three groups were either subjected to a nonconditioning (aerobic perfusion followed by 30-min coronary occlusion and 120-min reperfusion, i.e., test ischemia-reperfusion), preconditioning (three intermittent periods of 5-min ischemia-reperfusion cycles before test ischemia-reperfusion), or postconditioning (six cycles of 10-s ischemia-reperfusion after test ischemia) perfusion protocol. Preconditioning and postconditioning significantly decreased infarct size in vehicle-treated hearts. However, preconditioning failed to decrease infarct size in acute lovastatin-treated hearts, but the effect of postconditioning remained unchanged. Chronic lovastatin treatment abolished postconditioning but not preconditioning; however, it decreased infarct size in the nonconditioned group. Myocardial levels of coenzyme Q9 were decreased in both acute and chronic lovastatin-treated rats. Western blot analysis revealed that both acute and chronic lovastatin treatment attenuated the phoshorylation of Akt; however, acute but not chronic lovastatin treatment increased the phosphorylation of p42 MAPK/ERK. We conclude that, although lovastatin may lead to cardioprotection, it interferes with the mechanisms of cardiac adaptation to ischemic stress.
Authors:
Gabriella F Kocsis; Judit Pipis; Veronika Fekete; Andrea Kovács-Simon; Louise Odendaal; Eva Molnár; Zoltán Giricz; Tamás Janáky; Jacques van Rooyen; Tamás Csont; Péter Ferdinandy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-21
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  294     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-07     Completed Date:  2008-06-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2406-9     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Group and PharmaHungary Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Disease Models, Animal
Down-Regulation
Drug Administration Schedule
Enzyme Activation
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage,  pharmacology*
Ischemic Preconditioning, Myocardial*
Lovastatin / administration & dosage,  pharmacology*
Male
Mitogen-Activated Protein Kinase 1 / metabolism
Myocardial Infarction / metabolism,  pathology,  prevention & control*
Myocardial Reperfusion Injury / metabolism,  pathology,  prevention & control*
Myocardium / enzymology,  pathology*
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Wistar
Ubiquinone / metabolism
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 1339-63-5/Ubiquinone; 303-97-9/ubiquinone 9; 75330-75-5/Lovastatin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1

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