title: Excessive sympathoactivation and deteriorated heart function after myocardial infarction in male ghrelin knockout mice.
abstract: We have previously demonstrated the protective role of endogenous ghrelin against malignant arrhythmias in the very acute phase of myocardial infarction (MI). However, the role of endogenous ghrelin in the chronic phase is unknown. Therefore, the aim of the current study was to focus on the effects of endogenous ghrelin on cardiac function and sympathetic activation after acute MI. In 46 ghrelin-knockout (KO) and 41 wild-type (WT) male mice, MI was produced by left coronary artery ligation. The mortality due to heart failure within 2 weeks was 0% in WT and 10.9% in KO (P < 0.05). At the end of this period, lung weight/tibial length, atrial natriuretic peptide and brain natriuretic peptide transcripts, end-systolic and end-diastolic volumes were all significantly greater in KO mice, whereas systolic function, represented by ejection fraction (16.4 ± 4.7% vs 25.3 ± 5.1%), end-systolic elastance, and preload-recruitable stroke work, was significantly inferior to that in WT mice (P < 0.05). Telemetry recording and heart rate variability analysis showed that KO mice had stronger sympathetic activation after MI than did WT mice. Metoprolol treatment and ghrelin treatment in KO mice prevented excessive sympathetic activation, decreased plasma epinephrine and norepinephrine levels, and improved heart function and survival rate after MI. Our data demonstrate that endogenous ghrelin plays a crucial role in protecting heart function and reducing mortality after myocardial infarction, and that these effects seem to be partly the result of sympathetic inhibition.
authors.affiliation: Department of Biochemistry, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Mao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D013565:Sympatholytics / Q000494:pharmacology
chemical_list: D054439:Ghrelin; D013565:Sympatholytics; D008790:Metoprolol