Angiotensin II-Induced Ventricular Hypertrophy and Extracellular Signal-Regulated Kinase Activation Are Suppressed in Mice Overexpressing Brain Natriuretic Peptide in Circulation

• TAKAHASHI Nobuki

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• SAITO Yoshihiko

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• KUWAHARA Koichiro

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• HARADA Masaki

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• KISHIMOTO Ichiro

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• OGAWA Yoshihiro

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• KAWAKAMI Rika

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• NAKAGAWA Yasuaki

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• NAKANISHI Michio

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

• NAKAO Kazuwa

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine

抄録

Atrial and brain (B-type) natriuretic peptides (ANP and BNP, respectively) are known to exert various cardioprotective effects. For instance, knocking out the expression of ANP, BNP, or their receptor, guanylyl cyclase-A, induces cardiac hypertrophy and/or fibrosis. The cardiac effects of elevated circulating natriuretic peptides are less well understood, however. We therefore compared angiotensin (Ang) II-induced cardiac hypertrophy and fibrosis in BNP-transgenic (Tg) mice, in which circulating BNP levels were elevated by increased secretion from the liver, and their non-Tg littermates. Left ventricular expression of Ang II type 1a receptor was similar in BNP-Tg and non-Tg mice, and there was no significant difference in the elevation of blood pressure elicited by chronic infusion or acute injection of Ang II. Nevertheless, cardiac hypertrophy and fibrosis were significantly diminished in BNP-Tg mice chronically infused with Ang II. In addition, ventricular activation of extracellular signal-regulated kinase (ERK) induced by acute injection of Ang II was also diminished in BNP-Tg mice, as was activation of ERK kinase (MEK). Conversely, expression of mitogen-activated protein kinase phosphatase (MKP) was significantly increased in the ventricles of BNP-Tg mice. Based on these findings, we conclude that elevated circulating BNP exerts cardioprotective effects via inhibition of a ventricular ERK pathway. The mechanism responsible for this inhibition likely involves 1) increased ventricular MKP expression and 2) inhibition of transduction mediators situated upstream of ERK. (Hypertens Res 2003; 26: 847-853)

収録刊行物

• Hypertension Research

  Hypertension Research 26 (10), 847-853, 2003

  日本高血圧学会

キーワード

• <B>natriuretic peptide</B>
• <B>cardiac hypertrophy</B>
• <B>extracellular signal-regulated kinase</B>
• <B>angiotensin II</B>
• <B>transgenic mice</B>

詳細情報

• CRID: 1390001204720917376
• NII論文ID: 10012457798
• NII書誌ID: AA10847079
• DOI: 10.1291/hypres.26.847
• COI: 1:CAS:528:DC%2BD2cXis1KhtQ%3D%3D
• ISSN: 13484214
• ISSN: 09169636
• PubMed: 14621189
• Web Site: https://search.jamas.or.jp/link/ui/2004099624
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可