Role of cardiac nonmyocytes in cyclic mechanical stretch-induced myocyte hypertrophy

In cardiac hypertrophy or ventricular remodeling, not only the enlargement of myocytes but also interstitial or perivascular fibrosis are observed simultaneously, which suggests an interaction between cardiac myocytes and fibroblasts. In this study, we examined the mechanism of cyclic mechanical str...

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Bibliographic Details
Published in:Heart and vessels 1997, Vol.Suppl 12, p.198
Main Authors: Harada, M, Saito, Y, Nakagawa, O, Miyamoto, Y, Ishikawa, M, Kuwahara, K, Ogawa, E, Nakayama, M, Kamitani, S, Hamanaka, I, Kajiyama, N, Masuda, I, Itoh, H, Tanaka, I, Nakao, K
Format: Article
Language:English
Subjects:
Angiotensin Receptor Antagonists
Animals
Atrial Natriuretic Factor - analysis
Benzimidazoles - pharmacology
Cardiomegaly - pathology
Cardiomegaly - physiopathology
Cells, Cultured
Coculture Techniques
Endothelin Receptor Antagonists
Fibroblasts - pathology
Myocardium - cytology
Myocardium - pathology
Natriuretic Peptide, Brain
Nerve Tissue Proteins - analysis
Peptides, Cyclic - antagonists & inhibitors
Rats
Stress, Mechanical
Tetrazoles - pharmacology
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Summary:In cardiac hypertrophy or ventricular remodeling, not only the enlargement of myocytes but also interstitial or perivascular fibrosis are observed simultaneously, which suggests an interaction between cardiac myocytes and fibroblasts. In this study, we examined the mechanism of cyclic mechanical stretch-induced myocyte hypertrophy, highlighting the interaction between myocytes and cardiac nonmyocytes, mostly fibroblasts. Ventricular myocytes (MC) and cardiac nonmyocytes (NMC) were separately extracted from neonatal rat ventricles by the discontinuous Percoll gradient method and primary cultures of cardiac cells were prepared. Cyclic mechanical stretch was applied to the cultures with a Flexercell Stress Unit. In addition to cell size, we examined atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP) production as the most sensitive biological markers for MC hypertrophy. Cyclic stretch did not induce hypertrophic responses in MC when they were cultured without NMC. In contrast, when MC were co-cultured with NMC, cyclic stretch induced further increase in ANP/BNP production (2.2-fold and 2.1-fold increases versus non-stretch group, after 48-h incubation). This increase in ANP/BNP production in the co-culture was significantly suppressed by CV-11974, an angiotensin II type 1 receptor antagonist. Moreover, ANP/BNP production in the co-culture was significantly suppressed by BQ-123, an endothelin A receptor antagonist, whether cyclic stretch was applied or not. This study raised the possibility that NMC mediate the hypertrophic effect of mechanical stress on MC by increasing endothelin production. It was also suggested that, in this process, angiotensin II is involved in the crosstalk between MC and NMC.
ISSN:0910-8327