Objective: The mammalian heart contains specific growth hormone-releasing peptide (GHRP) binding sites whose physiological significance is unknown. We sought to compare the effects of GHRP and GH on progressive left ventricular (LV) dysfunction in the TO-2 hamster model of dilated cardiomyopathy. Methods: TO-2 hamsters (8 weeks old) were injected with GHRP-6 (100 μg/kg day), GH (2 mg/kg day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and structural changes were evaluated by echocardiography and pathology. Results: The increase in body weight of GH-treated TO-2 hamsters was greater than that of animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF-1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS) decreased from 42.0±2.6% to 25.4±1.8% and the LV end-diastolic dimension (LVDd) increased from 4.0±0.1 to 5.0±0.1 mm in untreated TO-2 hamsters between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6 (33.4±2.0%) or GH (32.0±2.1%). The LVDd was significantly smaller in animals treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte area and the amount of atrial natriuretic peptide mRNA in the LV were increased by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day)) exerted minimal cardiac and systematic growth effects without improving LV function. Conclusion: GHRP can ameliorate the development of progressive LV dysfunction independently of the GH-IGF-1 axis, suggesting a potential new approach to the heart failure.
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