Contractile effects of Ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium.
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.
Soares
João-Bruno
JB
Serviço de Fisiologia da Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Rocha-Sousa
Amândio
A
Castro-Chaves
Paulo
P
Henriques-Coelho
Tiago
T
Lourenço
André Pedro
AP
Roncon-Albuquerque
Roberto
R
Leite-Moreira
Adelino F
AF
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
D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone