title: Growth hormone- and pressure overload-induced cardiac hypertrophy evoke different responses to ischemia-reperfusion and mechanical stretch.
abstract: OBJECTIVE
  To compare the molecular, histological, and functional characteristics of growth hormone (GH)- and pressure overload-induced cardiac hypertrophy, and their responses to ischemia-reperfusion and mechanical stretch.
  
  
  METHODS
  Four groups of male Wistar rats were studied: aortic banding (n=24, AB) or sham (n=24, controls) for 10 weeks, and GH treatment (n=24; 3.5mg/kg/day, GH) or placebo (n=24, controls) for 4 weeks. At 13 weeks, the rats were randomly subjected to: (i) assessment of basal left ventricular mRNA expression of sarcoplasmic reticulum calcium-ATPase (SERCA-2), phospholamban (PLB), and Na(+)-Ca(2+) exchanger (NCX) and collagen volume fraction (CVF) (Protocol A, 8 rats in each group); (ii) left ventricular no-flow ischemia with simultaneous evaluation of intracellular Ca(2+) handling and ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) content (Protocol B, 12 rats in each group); or (iii) left ventricular mechanical stretch for 40 min with assessment of tumor necrosis-alpha (TNF-alpha) mRNA (Protocol C, 4 rats in each group). Protocol B and C were carried out in a Langendorff apparatus.
  
  
  RESULTS
  In Protocol A, no difference was found as to myocardial mRNA content of Ca(2+) regulating proteins and CVF in GH animals vs controls. In contrast, in the AB group, myocardial mRNA expression of SERCA-2 and PLB was downregulated while that of NCX and CVF were increased vs. controls (p<0.05). In Protocol B, recovery of left ventricular function was significantly decreased in AB vs GH groups and controls and this was associated with 1.6-fold increase in intracellular Ca(2+) overload during reperfusion (p<0.05). Baseline ATP content was similar in the four study groups, whereas PCr and Pi was lower in AB vs GH rats and controls. However, the time courses of high-energy phosphate metabolic changes did not differ during ischemia and reperfusion in the four study groups. In Protocol C, no detectable TNF-alpha mRNA level was found in the left ventricular myocardium of GH treated rats and controls at baseline, while a modest expression was noted in AB animals. Mechanical stretch resulted in de novo myocardial TNF-alpha mRNA expression in GH group and controls, which was dramatically increased in AB animals ( approximately 5-fold above baseline, p<0.001).
  
  
  CONCLUSIONS
  The data show that cardiac hypertrophy activated by short-term GH treatment confers cardioprotection compared with pressure overload with regard to molecular and histological characteristics, and responses to ischemia-reperfusion and mechanical stretch.
authors.affiliation: Department of Medicine, Medizinische Universitätsklinik Würzburg, 97080 Würzburg, Germany.
authors.forename: Hinrik
authors.initials: H
authors.lastname: Strömer
authors.forename: Emiliano A
authors.initials: EA
authors.lastname: Palmieri
authors.forename: Mark C H
authors.initials: MC
authors.lastname: De Groot
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Rella
authors.forename: Andrea
authors.initials: A
authors.lastname: Leupold
authors.forename: Michael
authors.initials: M
authors.lastname: Horn
authors.forename: Maria G
authors.initials: MG
authors.lastname: Monti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Napoli
authors.forename: Angela
authors.initials: A
authors.lastname: Di Gianni
authors.forename: Jörgen
authors.initials: J
authors.lastname: Isgaard
authors.forename: Luigi
authors.initials: L
authors.lastname: Saccà
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011312:Pressure / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D010710:Phosphates; D013006:Growth Hormone; D002118:Calcium