Therapy with the Nonpeptide Endothelin Receptor Antagonist 97-139 in a Murine Model of Congestive Heart Failure Reduction of Cardiac Mass and Myofiber Hypertrophy

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概要

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• Endothelin-1 (ET-1) is a potent vasoconstrictor. This peptide exerts numerous effects on the heart, including regulation of cardiomyocyte growth during hypertrophy. The effects of the structurally novel, nonpeptide, ET-1-selective, competitive antagonist (ETA) 97-139 were investigated in mice with congestive heart failure (CHF) and myocardial hypertrophy. Morphological and microscopical analyses were conducted on day 56 after viral inoculation following 28 day treatment with 99-139. Eight week-old DBA2 mice were intraperitoneally inoculated with encephalomyocarditis virus at a dose of 500 pfu/mouse. The 30 mice were divided into two groups-an ETA treated group and an untreated group. Heart weight (HW) in the infected group was significantly (p<0.05) increased compared to that in the uninfected group. HW and the HW/body weight (BW) ratio were significantly (p<0.05) reduced in the ETA treated group compared with the untreated group (HW; 127.7±6.2mg vs 144.3±4.2 mg, HW/BW; 4.9±0.9×10-3 vs 5.4±0.5×10-3). Myofiber diameter in the ETA treated group was significantly reduced compared with the untreated group (12.1±1.5μm vs 14.3±1.9μm). These results suggest the ET-1 receptor antagonist 97-139 has an effect on the reduction of cardiac mass and myofiber hypertrophy, and that 97-139 may be a useful agent for CHF due to viral myocarditis. (Jpn Heart J 2000; 41: 79-85)

著者

• Arai Masashi

  Second Department Internal Medicine, Gunma University School Of Medicine

• Seta Yukihiro

  Second Department of Internal Medicine

• Sekiguchi Ken-ichi

  Second Department Of Inernal Medicine Gunma University School Of Medicine

• Kanda Tsugiyasu

  Second Department Of Internal Medicine Gunma University

• Nagai Ryozo

  Second Department Of Internal Medicine And Health Science Gunma University School Of Medicine

• SETA Yukihiro

  Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.

• YOKOYAMA Tomoyoshi

  Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.

• TANAKA Tohru

  Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.

• KOBAYASHI Isao

  Second Department of Internal Medicine, Department of Laboratory Medicine, Gunma University School of Medicine, Gunma, Japan.

• SEKIGUCHI Ken-ichi

  Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.

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