title: Hexarelin treatment in male ghrelin knockout mice after myocardial infarction.
abstract: Both ghrelin and the synthetic analog 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/d, sc) 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 < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), 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.affiliation: Department of Biochemistry, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. kishimot@hsp.ncvc.go.jp.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Mao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nagai
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004452:Echocardiography; D054439:Ghrelin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009842:Oligopeptides / Q000627:therapeutic use*; D055550:Protein Stability; D013318:Stroke Volume / Q000187:drug effects; D016019:Survival Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D054439:Ghrelin; D009842:Oligopeptides; C086184:hexarelin