title: Contractile effects of Ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium.
abstract: BACKGROUND
  Ghrelin, isolated in 1999, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Recent studies suggest that it may influence the function of normal and failing hearts. Nonetheless, it has been difficult to differentiate its effects on the intrinsic properties of the myocardium from the secondary effects resulting from growth hormone release and vasomotor action. This study investigated the contractile effects of ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium.
  
  
  METHODS
  Adult Wistar rats randomly received monocrotaline (MCT; n=9; 60 mg/kg, s.c.) or vehicle (n=7; 1 ml/kg). Three weeks later, after right ventricular (RV) hemodynamic evaluation, the effects of 10(-6) M of a pentapeptide active fragment of ghrelin (fG) were tested on contractile parameters of RV papillary muscles (Normal, n=7; MCT, n=9). GHS-R1a mRNA expression was estimated in RV transmural free-wall samples (Normal, n=7; MCT, n=9), using real-time RT-PCR.
  
  
  RESULTS
  In the Normal group, fG reduced active tension (AT), maximum velocity of tension rise (dT/dt(max)) and maximum velocity of tension decline (dT/dt(min)), by 27.9 +/- 4.0%, 28.5 +/- 6.7% and 21.4 +/- 4.2% respectively. In the MCT group, fG reduced AT, dT/dt(max) and dT/dt(min) by 24.1 +/- 6.3%, 24.3 +/- 6.5% and 24.5 +/- 6.1% respectively. GHS-R1a mRNA expression was similar in the two groups (Normal: 2.3*10(5) +/- 5.4*10(4); MCT: 3.0*10(5) +/- 1.1*10(5): p > 0.05).
  
  
  CONCLUSIONS
  This study shows that ghrelin has negative inotropic and lusitropic effects. These effects and expression of its receptor are preserved in RV hypertrophy, suggesting that ghrelin may be a new target in progression to heart failure.
authors.affiliation: Serviço de Fisiologia da Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
authors.forename: João-Bruno
authors.initials: JB
authors.lastname: Soares
authors.forename: Amândio
authors.initials: A
authors.lastname: Rocha-Sousa
authors.forename: Paulo
authors.initials: P
authors.lastname: Castro-Chaves
authors.forename: Tiago
authors.initials: T
authors.lastname: Henriques-Coelho
authors.forename: André Pedro
authors.initials: AP
authors.lastname: Lourenço
authors.forename: Roberto
authors.initials: R
authors.lastname: Roncon-Albuquerque
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000818:Animals; D054439:Ghrelin; D013006:Growth Hormone / Q000502:physiology*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D036361:Peptide Hormones / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D054440:Receptors, Ghrelin
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone