title: Cyclosporin A does not block exercise-induced cardiac hypertrophy.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Tess
authors.initials: T
authors.lastname: Hainsey
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Shuangdan
authors.initials: S
authors.lastname: Sun
authors.forename: John G
authors.initials: JG
authors.lastname: Edwards
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000032:analysis; D006333:Heart Failure / Q000188:drug therapy; D006334:Heart Function Tests; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010805:Physical Conditioning, Animal; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D016572:Cyclosporine; D003576:Electron Transport Complex IV