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Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters

Tsukasa Inada, MD^*, Hisayoshi Fujiwara, MD^*, Koji Hasegawa, MD^*, Makoto Araki, MD^*, Rikako Yamauchi-Kohno, MS, Hideo Yabana, PhD, Takako Fujiwara, MD, Masaru Tanaka, MD^* and Shigetake Sasayama, MD, FACC^*

^* Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan
Lead Optimization Research Laboratory, Tanabe Seiyaku, Saitama, Japan
Department of Food Science, Kyoto Women’s University, Kyoto, Japan

View larger version (10K): [in a new window]   Figure 1 Cardiac (A) and pulmonary (B) ET-1 levels in Bio 14.6 Syrian cardiomyopathic hamsters (Bio-CTL) compared with F1B controls (F1B-CTL). Cardiac and pulmonary ET-1 levels were measured by a specific sandwich EIA as described in Materials and Methods. Values are mean ± SEM. (A) #p < 0.0001 vs. age-matched F1B-CTL, 5-week old Bio and 20-week old Bio-CTL. *p < 0.0005 vs. age-matched F1B-CTL. (B) **p < 0.005 vs. age-matched F1B-CTL, 5-week old Bio-CTL and 20-week old Bio-CTL. Open squares = F1B; solid squares = Bio.

View larger version (7K): [in a new window]   Figure 2 Immunohistochemical detection of ET-1 in the left ventricles of 35 week-old Bio14.6 cardiomyopathic (A and B) and age-matched control F1B (C) hamsters. Immuno-reactive ET-1 was detected with an indirect peroxidase method as described in Materials and Methods. Preincubating an excess of synthetic ET-1 with a primary antibody resulted in no staining (B). Original magnification x 200.

View larger version (31K): [in a new window]   Figure 3 The effects of ET type A receptor antagonist T0201 on heart/body weight ratio in Bio and F1B. An oral administration of the ET type A receptor antagonist T0201 was started at five weeks of age in Bio and F1B hamsters. Values are mean ± SEM.

View larger version (27K): [in a new window]   Figure 4 The effects of ET type A receptor antagonist T0201 on fibrosis (A) and myocyte diameter (B) in the left ventricles of Bio and F1B. Values are mean ± SEM.