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. Design. 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; 3.5 mg/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-α (TNF-α) 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-α 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-α mRNA expression in GH group and controls, which was dramatically increased in AB animals (≈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.

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