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Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction.
MedLine Citation:
PMID:  23861368     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Both ghrelin and the synthetic analogue hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin knockout mice, and to compare the effects of hexarelin (400 nmol/kg per day, s.c.) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < 0.05). A comparison of cardiac function 2 weeks post-infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output were greater, while systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min, were significantly superior compared to the vehicle group (P < 0.05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max, and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin knockout mice, although both hormones have similar effects on heart rate variability and mortality.
Authors:
Yuanjie Mao; Takeshi Tokudome; Ichiro Kishimoto; Kentaro Otani; Hiroshi Hosoda; Chiaki Nagai; Naoto Minamino; Mikiya Miyazato; Kenji Kangawa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-16
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry (Y.M., T.T., I.K., M.M., and K.K.), Department of Regenerative Medicine and Tissue Engineering (K.O. and H.H.), Department of Molecular Pharmacology (C.N. and N.M.), National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
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