title: One dose of oral hexarelin protects chronic cardiac function after myocardial infarction.
abstract: Both hexarelin and its natural analog ghrelin exert comparable cardioprotective activities. A single dose of ghrelin administered at the very acute phase after experimental myocardial infarction positively affects cardiac function in chronic heart failure. Therefore, this study aimed to determine whether a single dose of oral hexarelin has the same effect in the chronic disease phase. Myocardial infarction or sham operation was generated by left coronary artery ligation in male C57BL/6J mice, which subsequently received one dose of hexarelin or vehicle treatment by oral gavage 30 min after operation. Although the mortality within 14 days after myocardial infarction did not differ between the groups, hexarelin treatment protected cardiac function in the chronic phase as evidenced by higher ejection fraction and fractional shortening, as well as lower lung weight/body weight and lung weight/tibial length ratios, compared with vehicle treatment. Hexarelin treatment concurrently lowered plasma epinephrine and dopamine levels, and shifted the balance of autonomic nervous activity toward parasympathetic nervous activity as evidenced by a smaller low/high-frequency power ratio and larger normalized high-frequency power on heart rate variability analysis. The results first demonstrate that one dose of oral hexarelin treatment potentially protects chronic cardiac function after acute myocardial infarction, and implicate that activating growth hormone secretagogue receptor 1a might be beneficial for cardioprotection, although other mechanism may also be involved.
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan. Electronic address: kishimot@hsp.ncvc.go.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy*; D009638:Norepinephrine / Q000097:blood; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D009842:Oligopeptides; C086184:hexarelin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine
keywords: Cardiac function; Hexarelin; Myocardial infarction; Sympathetic nerve