Abstract
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The effect of Intermedin on Angiotensin II and Endothelin-1 Induced Ventricular Myocyte Hypertrophy in Neonatal Rat
by Kai Liu, Xiaoming Deng, Ling Gong, Xiaoping Chen, Si Wang, Hongying Chen, Xiaoni Chen, Bogati Amrit, Sen He
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Background: Intermedin (IMD), a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), may have localized 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 myocytes of neonatal rat and to try to elucidate the possible mechanism.
Methods: Neonatal rat cardiomyocytes were cultured in serum-free medium with and without AngII (1 μmol/L) or ET-1 (60 μmol/L) in the presence and absence of IMD (1 μmol/L). Hypertrophic responses (including 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 48 hours), alphaactin expression to 4 ± 2.8-fold (n = 6, p < 0.05, at 48 hours) and β-myosin heavy chain expression to 11 ± 4.8-fold (n = 6, p < 0.05, at 48 hours), and expression of the gp91phox subunit of NADPH oxidase to 29.4 ± 12.7-fold (n = 6, p < 0.05, at 48 hours). 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 ± 32 μm2 (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 that an antioxidant action contributes to the antihypertrophic actions of IMD.
DOI: 10.7754/Clin.Lab.2012.120708
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