title: Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters.
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 microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daiko Minami, Higashi, Nagoya 461-8673, Japan. iwase@met.nagoya-u.ac.jp
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Iwase
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kato
authors.forename: Takao
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Fuji
authors.initials: F
authors.lastname: Somura
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ishiki
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
authors.forename: Katsunori
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000032:analysis; D018450:Disease Progression; D013006:Growth Hormone / Q000097:blood / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008647:Mesocricetus; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000627:therapeutic use*; D049031:Sarcoglycans; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D049031:Sarcoglycans; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D013006:Growth Hormone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases