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GW24-e0068 The effect of intermedin on angiotensin II and endothelin-1 induced ventricular myocyte hypertrophy in neonatal rat
  1. Chen Xiaoping,
  2. Liu Kai
  1. Department of Cardiology, West China Hospital, Sichuan University


Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), which may have localised actions as a modulator of cardiac function. The aim of the study is to explore the effect of IMD on angiotensin II (Ang II) and endothelin-1(ET-1) induced hypertrophy in ventricular myocyte of neonatal rat, and try to elucidate the possible mechanism.

Methods Neonatal rat cardiomyocytes were cultured in serum-free medium with and without Ang II (1 μmol/L) or ET-1(60 μmol/L) in the presence and absence of IMD (1 μmol/L). Hypertrophic responses (include cell surface area, alpha-actin and β-myosin heavy chain mRNA expression) and cardiomyocyte expression of NADPH oxidase gp91phox were determined.

Results Ang II induced increases in cardiomyocyte size (to 305 ± 32 μm2 n = 198, p < 0.05, at 48h), alpha-actin expression (to 4 ± 2.8-fold n = 6 p < 0.05, at 48h) and β-myosin heavy chain expression (to 11 ± 4.8-fold n = 6 p < 0.05, at 48h), and expression of the gp91phox subunit of NADPH oxidase (to 29.4 ± 12.7-fold n = 6 p < 0.05, at 48h). These effects were all significantly inhibited by IMD; cardiomyocyte size, alpha-actin expression, β-myosin heavy chain expression and gp91phox expression were reduced to 265 ± 32μm2 (n = 374, P < 0.05), 3.0 ± 1.7-fold (n = 6 p < 0.05), 8.7 ± 4.9-fold (n = 6 p < 0.05), 3.9 ± 3-fold (n = 6 p < 0.05), respectively. IMD also significantly inhibited ET1-induced increases in cardiomyocyte size and superoxide generation.

Conclusions IMD exerts an antihypertrophic effect on neonatal cardiomyocytes by reduced levels of superoxide, suggesting an antioxidant action contributes to the antihypertrophic actions of IMD.

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