Overexpression of Endothelial Nitric Oxide Synthase Attenuates Cardiac Hypertrophy Induced by Chronic Isoproterenol Infusion

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概要

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• Endogenous nitric oxide (NO) inhibits the contractile response to ★-adrenergic stimulation, but its effect on cardiac hypertrophy mediated by ★-adrenoceptors remains unclear. The present study was designed to determine whether overproduction of endothelial NO synthase (eNOS) could inhibit cardiac hypertrophy induced by chronic isoproterenol (ISO) infusion (30 mg/kg per day) using eNOS overexpressing (eNOS-Tg) mice and wild-type (WT) mice. In a separate group, WT mice were treated with ISO and hydralazine to decrease blood pressure to the same levels in eNOS-Tg mice. The eNOS expression, NOS activity, and cGMP levels in the heart were remarkably higher in eNOS-Tg mice than in WT mice. ISO increased both heart weight and the heart/body weight ratio, which were significantly attenuated in eNOS-Tg mice compared with WT or hydralazine-treated WT mice. Histological examination revealed that the extent of fibrosis was not significantly different among the 3 groups, and that the increase in myocyte size was more than 10% lower in eNOS-Tg than in the other groups. In addition, up-regulated expression of atrial natriuretic peptide mRNA associated with cardiac hypertrophy was significantly inhibited in eNOS-Tg mice during ISO infusion. These results indicate that endogenous NO might act as a negative modulator for the hypertrophic response to ★-adrenergic stimulation.

• 2002-08-20

著者

• YOKOYAMA Mitsuhiro

  Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe Universit

• OZAKI Masanori

  Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osak

• Ozaki Masanori

  Division Of Cardiovascular And Respiratory Medicine Department Of Internal Medicine Kobe University

• HIRATA Ken-ichi

  Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate Schoo

• Yokoyama Mitsuhiro

  Division Of Cardiovascular And Respiratory Medicine Department Of Internal Medicine Kobe University

• Kawashima Seinosuke

  Division Of Cardiovascular And Respiratory Medicine Kobe University Graduate School Of Medicine

• Ohashi Yoshitaka

  Division of Cardiology, Miki General Hospital

• Ohashi Yoshitaka

  Division Of Cardiology Miki General Hospital

• Yamashita Tomoya

  Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate Schoo

• Inoue Nobutaka

  Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine

• Hirase Tetsuaki

  Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine

• Kawashima Seinosuke

  Division Of Cardiovascular And Respiratory Medicine Department Of Internal Medicine Kobe University

• Hirata Ken-ichi

  Division Of Cardiovascular Medicine Department Of Internal Medicine Kobe University Graduate School

• Yamaguchi Tsutomu

  Division Of Cardiovascular Medicine Kobe University Graduate School Of Medicine

• Yamashita Tomoya

  Division Of Cardiovascular And Respiratory Medicine Kobe University Graduate School Of Medicine

• Hirase Tetsuaki

  Division Of Cardiovascular And Respiratory Medicine Department Of Internal Medicine Kobe University

• Hirata Ken-ichi

  Department Cardiology Kobe University Graduate School Of Medicine

• Ohhashi Yoshitaka

  Department Of Cardiology Miki City Hospital

• Yasuda Tomoyuki

  Division Of Cardiovascular Medicine Kobe University Graduate School Of Medicine

• Hirase Tetsuaki

  Kobe University Graduate School of Medicine

• Inoue Nobutaka

  Division Of Cardiovascular And Respiratory Department Of Internal Medicine Kobe University School Of

• Oohashi Yoshitaka

  Department Of Cardiology Miki City Hospital

• Oohashi Yoshitaka

  Division Of Cardiology Miki General Hospital

• HIRATA Ken-ichi

  Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine

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