Growth hormone- and pressure overload-induced cardiac hypertrophy evoke different responses to ischemia-reperfusion and mechanical stretch.
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.
Strömer
Hinrik
H
Department of Medicine, Medizinische Universitätsklinik Würzburg, 97080 Würzburg, Germany.
Palmieri
Emiliano A
EA
De Groot
Mark C H
MC
Di Rella
Francesca
F
Leupold
Andrea
A
Horn
Michael
M
Monti
Maria G
MG
Napoli
Raffaele
R
Di Gianni
Angela
A
Isgaard
Jörgen
J
Saccà
Luigi
L
Neubauer
Stefan
S
Cittadini
Antonio
A
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*
D010710:Phosphates; D013006:Growth Hormone; D002118:Calcium