Beneficial effects of growth hormone-releasing peptide on myocardial oxidative stress and left ventricular dysfunction in dilated cardiomyopathic hamsters.
BACKGROUND
Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, suggesting a potential new approach to the treatment of cardiomyopathic hearts. The present study tested the hypothesis that the beneficial cardiac effects of GHRP might include attenuation of myocardial oxidative stress.


RESULTS
Dilated cardiomyopathic TO-2 hamsters were injected with GHRP-2 (1 mg/kg) or saline from 6 to 12 weeks of age. F1B hamsters served as controls. Untreated TO-2 hamsters progressively developed LV dilation, wall thinning, and systolic dysfunction between 6 and 12 weeks of age. Marked myocardial fibrosis was apparent in untreated hamsters at 12 weeks of age in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and the concentration of 4-hydroxynonenal (4-HNE) was increased in the hearts of untreated TO-2 hamsters. Treatment with GHRP-2 attenuated the progression of LV remodeling and dysfunction, as well as myocardial fibrosis, in TO-2 hamsters. GHRP-2 also inhibited both the decrease in the GSH/GSSG ratio and the increase in the concentration of 4-HNE in the hearts of TO-2 hamsters.


CONCLUSIONS
GHRP-2 can suppress the increase in the level of myocardial oxidative stress, leading to attenuation of progressive LV remodeling and dysfunction in dilated cardiomyopathic hamsters. (Circ J 2010; 74: 163 - 170).
Kato
Yosuke
Y
Pathophysiological Laboratory Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Iwase
Mitsunori
M
Ichihara
Sahoko
S
Kanazawa
Hiroaki
H
Hashimoto
Katsunori
K
Noda
Akiko
A
Nagata
Kohzo
K
Koike
Yasuo
Y
Yokota
Mitsuhiro
M
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D049031:Sarcoglycans / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D000447:Aldehydes; D009842:Oligopeptides; D049031:Sarcoglycans; C091874:growth hormone-releasing peptide-2; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D019803:Glutathione Disulfide