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

Mitsunori Iwase, Hiroaki Kanazawa, Yosuke Kato, Takao Nishizawa, Fuji Somura, Ryoji Ishiki, Kohzo Nagata, Katsunori Hashimoto, Kenji Takagi, Hideo Izawa, Mitsuhiro Yokota

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalCardiovascular Research
Volume61
Issue number1
DOIs
Publication statusPublished - 01-01-2004

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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