© 1995 American Heart Association, Inc.
Articles |
Angiotensin II Partly Mediates Mechanical Stress–Induced Cardiac Hypertrophy
From the Third Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Correspondence to Issei Komuro, The Third Department of Medicine, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. E-mail komuro-tky@umin.u-tokyo.ac.jp.
Abstract We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress–induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor–specific antagonist), and PD123319 (a type 2 receptor–specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress–induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.
Key Words: CV-11974 • signal transduction • MAP kinase • saralasin
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Y. Zou, I. Komuro, T. Yamazaki, R. Aikawa, S. Kudoh, I. Shiojima, Y. Hiroi, T. Mizuno, and Y. Yazaki Protein Kinase C, but Not Tyrosine Kinases or Ras, Plays a Critical Role in Angiotensin II-induced Activation of Raf-1 Kinase and Extracellular Signal-regulated Protein Kinases in Cardiac Myocytes J. Biol. Chem., December 27, 1996; 271(52): 33592 - 33597. [Abstract] [Full Text] [PDF]
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K. Kijima, H. Matsubara, S. Murasawa, K. Maruyama, Y. Mori, N. Ohkubo, I. Komuro, Y. Yazaki, T. Iwasaka, and M. Inada Mechanical Stretch Induces Enhanced Expression of Angiotensin II Receptor Subtypes in Neonatal Rat Cardiac Myocytes Circ. Res., October 1, 1996; 79(4): 887 - 897. [Abstract] [Full Text]
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T. Yamazaki, I. Komuro, S. Kudoh, Y. Zou, I. Shiojima, Y. Hiroi, T. Mizuno, K. Maemura, H. Kurihara, R. Aikawa, et al. Endothelin-1 Is Involved in Mechanical Stress-induced Cardiomyocyte Hypertrophy J. Biol. Chem., February 9, 1996; 271(6): 3221 - 3228. [Abstract] [Full Text] [PDF]
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F. Liang, A. Atakilit, and D. G. Gardner Integrin Dependence of Brain Natriuretic Peptide Gene Promoter Activation by Mechanical Strain J. Biol. Chem., June 30, 2000; 275(27): 20355 - 20360. [Abstract] [Full Text] [PDF]
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M. Sano, K. Fukuda, H. Kodama, J. Pan, M. Saito, J. Matsuzaki, T. Takahashi, S. Makino, T. Kato, and S. Ogawa Interleukin-6 Family of Cytokines Mediate Angiotensin II-induced Cardiac Hypertrophy in Rodent Cardiomyocytes J. Biol. Chem., September 15, 2000; 275(38): 29717 - 29723. [Abstract] [Full Text] [PDF]
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K. Tamura, Y. E. Chen, M. Lopez-Ilasaca, L. Daviet, N. Tamura, T. Ishigami, M. Akishita, I. Takasaki, Y. Tokita, R. E. Pratt, et al. Molecular Mechanism of Fibronectin Gene Activation by Cyclic Stretch in Vascular Smooth Muscle Cells J. Biol. Chem., October 27, 2000; 275(44): 34619 - 34627. [Abstract] [Full Text] [PDF]
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H. Uozumi, Y. Hiroi, Y. Zou, E. Takimoto, H. Toko, P. Niu, M. Shimoyama, Y. Yazaki, R. Nagai, and I. Komuro gp130 Plays a Critical Role in Pressure Overload-induced Cardiac Hypertrophy J. Biol. Chem., June 15, 2001; 276(25): 23115 - 23119. [Abstract] [Full Text] [PDF]
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