Exogenous administration of ghrelin modulates its myocardial levels and increases SERCA2a myocardial expression.

• Type: Summary of Presentation in an International Conference
• Date: 2005

Authors

Henriques-Coelho T (Author) FMUP; Roncon-Albuquerque R Jr (Author) FMUP; Lourenço AP (Author) FMUP; Teles A (Author) FMUP; Oliveira SM (Author) FMUP; Brandao-Nogueira A (Author) Other; Correia-Pinto J (Author) FMUP; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Journal of Heart Failure

Pages: 70-71

ESC Annual Congress 2005

Stockholm, Sweden , 03 a 07 de Setembro de 2005

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Ghrelin(Ghr) is a peptide with several cardiovascular effects. We recently shown that exogenous administration of ghrelin attenuates monocrotaline (MCT) induced pulmonary hypertension (PH) and ameliorates right and left hemodynamics. In order to clarify the mechanism underlying the beneficial myocardial effects induced by Ghr, we measured myocardial gene expression of IGF-1, Ghr and SERCA2a in MCT model. Adult Wistar rats were injected with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, animals were randomly divided and treated with Ghr (100 μg/kg, BID, sc) or with a similar volume of vehicle. The study resulted in 4 groups: (i) Sham (n=7), (ii) Sham+Ghr (n=7), (iii) MCT (n=9), (iv) MCT+Ghr (n=9). At days 21-25 the animals were instrumented to record RV and LV peak systolic (Psys) pressures, dP/dtmax and time constant Tau. RV and LV transmural freewall samples were collected to quantify, by real time RT-PCR, Ghr, IGF-1 and SERCA2a mRNA levels, which were normalized for GAPDH and expressed in arbitrary units (AU). Results, presented as mean±SEM, are summarized in Table 1 (P<0.05: a vs Sham; b vs Sham+Gr; c vs MCT). Table 1 RV-Sham RV-Sham RV-MCT RV-MCT LV-Sham LV-Sham LV-MCT LV-MCT + Ghr + Ghr + Ghr + Ghr Psys 25.1 20.4 48.2 a 35.9 99.4 109.7 67.4 85.0 (mmHg) ±1.7 ±1.0 ±1.6 a ±1.9 a,b ±4.9 ±2.1 ±3.5 a ±4.2 a,b,c dP/dtmax 1228 1139 1602 1692 5624 7297 3442 a 5510 (mmHg/s) ±67 ±185 ±91 a ±113 a ±631 ±351 a ±325 a ±604 b,c Tau (ms) 7±1 11±1 28±2 a 17±2 a,b 18±1 14±1 22±1 16±2 c SERCA2a 1 1.75 0.31 0.65 1 1.54 0.98 1.83 (AU) ±0.2 ±0.3 a ±0.08 ±0.1 a,b,c ±0.2 ±0.2 a ±0.2 ±0.3 a,c IGF-1 1.0 1.6 4.9 1.9 1.0 1.3 1.4 1.3 (AU) ±0.2 ±0.2 ±0.2 a,b ±0.3 ±0.1 ±0.1 ±0.4 ±0.2 Ghrelin 1.0 0.04 20.6 28.5 1.0 0.39 0.42 a 0.22 (AU) ±0.3 ±0.04 a ±10.6 a,b ±11.5 a,b ±0.3 ±0.2 a ±0.2 a ±0.2 a Exogenous admnistration of Ghr improved both RV and LV hemodynamics and increased constitutive myocardial SERCA2a levels in in both ventricles. Myocardial levels of IGF-1 only increased in RV in MCT group confirming its dependence on ventricular overload. Myocardial expression of Ghr appears to be modulated by load because its levels are elevated on RV in MCT treated animals and decrease in LV. In conclusion, cardiac beneficial actions of Ghr seems to be independent from IGF-1 pathway and can be explained, at least in part, by modulation of SERCA2a myocardial levels.

Language: English

Type (Professor's evaluation): Scientific

Notes: 27th Congress of the European-Society-of-Cardiology, published in journal, European Heart Journal. 2005; Vol.26(Abstract. P562)(Suppl1):70-71.