Interaction of myocytes and nonmyocytes is necessary for mechanical stretch to induce ANP/BNP production in cardiocyte culture

Masaki Harada, Yoshihiko Saito, Koichiro Kuwahara, Emiko Ogawa, Masahiro Ishikawa, Osamu Nakagawa, Yoshihiro Miyamoto, Shigeki Kamitani, Ichiro Hamanaka, Noboru Kajiyama, Nobuki Takahashi, Izuru Masuda, Hiroshi Itoh, Kazuwa Nakao

研究成果: Article査読

56 被引用数 (Scopus)


In cardiac hypertrophy or ventricular remodeling, enlargement of myocytes and 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 myocytic hypertrophy, focusing on the interaction between myocytes and cardiac nonmyocytes, mostly fibroblasts. Ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs) were separately extracted from neonatal rat ventricles by the discontinuous Percoll gradient method and primary cultures of cardiac cells were prepared. When MCs were co-cultured with NMCs, the size of MCs and the ANP/BNP secretion were significantly increased. This hypertrophic change of MCs in the co-culture was significantly suppressed by BQ-123, an endothelin-A (ETA) receptor antagonist. Cyclic stretch did not induce hypertrophic responses in MC culture. However, it further increased ANP/BNP production in MC-NMC co-culture (2.2-fold and 2.1-fold increases vs. non-stretch group after 48-h incubation). This increase in ANP/BNP production in the coculture was significantly suppressed by CV-11974, an angiotensin II (Ang II) type 1 receptor antagonist. This study raises the possibility that NMCs regulate cardiocyte hypertrophy via secretion of endothelin-1 and that Ang II is involved in the interaction between MCs and NMCs during the course of hypertrophic response of cardiocytes to mechanical stretch.

ジャーナルJournal of Cardiovascular Pharmacology
出版ステータスPublished - 1998 1月 1

ASJC Scopus subject areas

  • 薬理学
  • 循環器および心血管医学


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