title: Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein.
abstract: Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.
authors.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, 2-50-1 Kuramoto, Tokushima, 770-8503, Japan, soeki@clin.med.tokushima-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Niki
authors.forename: Etsuko
authors.initials: E
authors.lastname: Uematsu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Bando
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuura
authors.forename: Kenya
authors.initials: K
authors.lastname: Kusunose
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ise
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Noriko
authors.initials: N
authors.lastname: Tomita
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Koshiba
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Daiju
authors.initials: D
authors.lastname: Fukuda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taketani
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwase
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamada
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Wakatsuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Akaike
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery
chemical_list: D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D054439:Ghrelin; C580592:Gja1 protein, rat; D018727:Muscarinic Antagonists; D001285:Atropine