Document Detail


Cyclosporin A does not block exercise-induced cardiac hypertrophy.
MedLine Citation:
PMID:  12165678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclosporin A (CsA) has been shown to inhibit pathophysiological models of overload-induced cardiac hypertrophy, indicating a role for the calcium dependent signal pathways. It is unclear what impact CsA may have on the myocardial response to exercise, a physiological model of overload.PURPOSE: The purpose of the study was to determine whether CsA would alter exercise-induced cardiac hypertrophy. METHODS: Thirty male rats were assigned to vehicle or CsA injection (15 mg.kg.d(-1)) and then assigned to sedentary or exercise training. Animals were swum for 60 min.d(-1) for 1 wk. RESULTS: One week of swim training significantly increased plantaris cytochrome oxidase activity, as well as significantly increasing left ventricular (LV) weight and the left ventricular:body weight (LV/BW) ratio. Exercise did not alter right ventricular (RV) weight or the RV/BW ratio. RNA analysis found that exercise significantly increased atrial natriuretic factor (ANF)-mRNA levels but did not influence alpha-myosin heavy chain (MHC) expression. CsA treatment, but not exercise, was associated with a significant increase in betaMHC expression. Western blot analysis determined that betaMHC protein was also significantly increased in the CsA-treated animals. CONCLUSION: CsA did not block exercise-induced cardiac hypertrophy but did significantly influence the myocardial phenotype. The CsA-sensitive calcium dependent pathways, important for pathological forms of overload-induced hypertrophy, were not essential to the early adaptations to exercise and that a different mechanism or signal transduction pathway was engaged. The data also indicate that CsA alone may induce a shift in the MHC isoform expression toward that associated with a pathological phenotype. Whether this phenotype shift contributes to the lowered exercise capacity found in transplant patients remains to be determined.
Authors:
Tess Hainsey; Anna Csiszar; Shuangdan Sun; John G Edwards
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Medicine and science in sports and exercise     Volume:  34     ISSN:  0195-9131     ISO Abbreviation:  Med Sci Sports Exerc     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-07     Completed Date:  2002-10-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8005433     Medline TA:  Med Sci Sports Exerc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1249-54     Citation Subset:  IM; S    
Affiliation:
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blotting, Western
Cyclosporine / pharmacology*
Disease Models, Animal
Electron Transport Complex IV / analysis
Heart Failure / drug therapy
Heart Function Tests
Hypertrophy, Left Ventricular / drug therapy*,  physiopathology
Male
Physical Conditioning, Animal
Probability
RNA, Messenger / analysis
Random Allocation
Rats
Rats, Sprague-Dawley
Reference Values
Treatment Outcome
Grant Support
ID/Acronym/Agency:
P01 HL 43023/HL/NHLBI NIH HHS; R29 HL 59417/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 59865-13-3/Cyclosporine; EC 1.9.3.1/Electron Transport Complex IV

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