| Lovastatin interferes with the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. | |
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MedLine Citation:
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PMID: 18359895 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-21 |
Journal Detail:
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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:
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Created Date: 2008-05-07 Completed Date: 2008-06-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2406-9 Citation Subset: IM |
Affiliation:
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Cardiovascular Research Group and PharmaHungary Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, Hungary. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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