title: Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction.
abstract: A recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether ghrelin administration would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via the suppression of cardiac sympathetic activity. Ghrelin (100 microg/kg sc, twice daily, n = 15) or saline (n = 15) were administered for 2 wk from the day after MI operation in Sprague-Dawley rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, histopathological, and gene analysis. In addition, before and after ghrelin (100 microg/kg sc, n = 6) was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. In ghrelin-treated rats, LV enlargement induced by MI was significantly attenuated compared with saline-treated rats. In addition, there was a substantial decrease in LV end-diastolic pressure and increases in the peak rate of the rise and fall of LV pressure in ghrelin-treated MI rats compared with saline-treated MI rats. Furthermore, ghrelin attenuated an increase in morphometrical collagen volume fraction in the noninfarct region, which was accompanied by the suppression of collagen I and III mRNA levels. Importantly, a 2-wk administration of ghrelin dramatically suppressed the MI-induced increase in heart rate and plasma norepinephrine concentration to the similar levels as in sham-operated controls. Moreover, acute administration of ghrelin to MI rats decreased the ratio of the low-to-high frequency spectra of heart rate variability (P < 0.01). In conclusion, these data suggest the potential usefulness of ghrelin as a new cardioprotective hormone early after MI.
authors.affiliation: National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita City, Osaka 565-8565, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Schwenke
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horio
authors.forename: Morikatsu
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000818:Animals; D001835:Body Weight; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D006339:Heart Rate; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D054439:Ghrelin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D009638:Norepinephrine