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Cardiovascular Research 2004 61(1):30-38; doi:10.1016/j.cardiores.2003.10.012
© 2004 by European Society of Cardiology
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Copyright © 2004, European Society of Cardiology

Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters

Mitsunori Iwase*,a, Hiroaki Kanazawaa, Yosuke Katoa, Takao Nishizawab, Fuji Somurac, Ryoji Ishikic, Kohzo Nagatac, Katsunori Hashimotoa, Kenji Takagia, Hideo Izawac and Mitsuhiro Yokotab

aDepartment of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daiko Minami, Higashi, Nagoya 461-8673, Japan
bCardiovascular Division, Department of Clinical Pathophysiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan
cDepartment of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan

* Corresponding author. Tel./fax: +81-52-719-1546. iwase{at}met.nagoya-u.ac.jp

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.

KEYWORDS Growth hormone-releasing peptide; Growth hormone; Cardiomyopathic hamsters; LV dysfunction

Time for primary review 23 days


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