title: Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats.
abstract: OBJECTIVE
  To determine the cardioprotective action of ghrelin and des-octanoyl ghrelin in rats with isoproterenol-induced myocardial injury.
  
  
  METHODS
  Rats were subcutaneously injected with isoproterenol (ISO; 20, 10, and 5 mg/kg) on d 1, 2 and 3, respectively, and then 3 mg/kg for the next 7 d with or without ghrelin or des-octanoyl-ghrelin (100 microg/kg, twice daily). Plasma ghrelin and growth hormone levels were assayed using radioimmunoassay methods. Growth hormone secretagogue receptor (GHSR) and ghrelin mRNA were determined using RT-PCR. The maximal binding capacity and the affinity for [3H]ghrelin were determined by receptor binding assays.
  
  
  RESULTS
  Compared with controls, ISO-treated rats showed severe myocardial injury, cardiomegaly, infarction-like necrosis and massive fibrosis with increases in irradiated-ghrelin (ir-ghrelin) content in plasma by 67% and myocardia by 66% and in the mRNA level in the myocardia by 93% (P<0.01). ISO-treated rats had 95% (P<0.01) higher GHSR mRNA levels in the myocardia. The maximal binding capacity of [3H]ghrelin for myocardial sarcolemma was higher in ISO-treated rats than in controls. Ghrelin administration improved cardiac function and ameliorated cardiomegaly and attenuated myocardial lipid peroxidation injury and relieved cardiac fibrosis as compared with ISO treatment alone. Administration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardial injury and improved all parameters measured. However, the therapeutic effect of des-octanoyl ghrelin was significantly weaker than that of ghrelin. The plasma growth hormone level increased markedly, by 1.5-fold (P<0.01), with ghrelin administration as compared with that in controls, but was unaltered in des-octanoyl ghrelin group.
  
  
  CONCLUSIONS
  Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial injury. The protective effect of ghrelin against ISO-induced cardiac function injury and fibrosis was more potent than that of des-octanoyl ghrelin, which suggests that ghrelin could be an endogenous cardioprotective factor in ischemic heart disease, and that its effects include growth hormone-dependent and -independent pathways.
authors.affiliation: Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: Zhang
authors.forename: Yong-Zheng
authors.initials: YZ
authors.lastname: Pang
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005355:Fibrosis; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood; D007545:Isoproterenol; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D036361:Peptide Hormones / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D054440:Receptors, Ghrelin; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D013006:Growth Hormone; D007545:Isoproterenol