Continuous Blockade of L-Type Ca2+ Channels Suppresses Activation of Calcineurin and Development of Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

• ZOU Yunzeng

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• YAMAZAKI Tsutomu

  Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine

• NAKAGAWA Keiichi

  Department of Radiology, University of Tokyo Graduate School of Medicine

• YAMADA Haruyasu

  Department of Radiology, University of Tokyo Graduate School of Medicine

• IRIGUCHI Norio

  Department of Biomedical Engineering, University of Tokyo Graduate School of Medicine

• TOKO Haruhiro

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• TAKANO Hiroyuki

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• AKAZAWA Hiroshi

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• NAGAI Ryozo

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• KOMURO Issei

  Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine

抄録

We examined whether Ca²⁺ channel blockers inhibit the activation of the Ca²⁺-dependent phosphatase calcineurin and the development of cardiac hypertrophy in spontaneously hypertensive rats (SHR). We randomly divided 12-week-old SHR into three groups, one each receiving vehicle, bolus injection or continuous infusion of nifedipine (10 mg⁄kg⁄day) from 12 to 24 weeks of age. Systolic blood pressure (BP) and heart rate were measured every week after the treatment using the tail-cuff plethysmography method. After 4, 8 and 12 weeks of treatment, 6 rats of each group were subjected to examinations that included an assay for calcineurin activity in the heart, magnetic resonance imaging (MRI), histology and Northern blot analysis. Continuous infusion of nifedipine consistently reduced BP, whereas bolus injection resulted in a fluctuation of BP. Continuous infusion of nifedipine not only reduced left ventricular mass but also decreased the transverse diameter of cardiomyocytes, interstitial fibrosis and the expression of the atrial natriuretic peptide and brain natriuretic peptide genes in the heart, while bolus injection of nifedipine did not significantly attenuate any of these hypertrophic responses in SHR. The activity of calcineurin in the heart was strongly suppressed by continuous but not bolus infusion of nifedipine in SHR. The results indicate that continuous blockade of Ca²⁺ channels with nifedipine effectively suppresses the development of cardiac hypertrophy in SHR, possibly through inhibition of the calcineurin activity. (Hypertens Res 2002; 25: 117-124)

収録刊行物

• Hypertension Research

  Hypertension Research 25 (1), 117-124, 2002

  日本高血圧学会

キーワード

• <B>Ca<SUP>2+</SUP></B>
• <B>calcineurin</B>
• <B>cardiac hypertrophy</B>
• <B>magnetic resonance imaging</B>
• <B>nifedipine</B>

詳細情報

• CRID: 1390001204720115712
• NII論文ID: 130004436943
• NII論文ID: 10009566997
• NII書誌ID: AA10847079
• DOI: 10.1291/hypres.25.117
• COI: 1:CAS:528:DC%2BD38XislCksbw%3D
• ISSN: 13484214
• ISSN: 09169636
• PubMed: 11924717
• Web Site: https://search.jamas.or.jp/link/ui/2002126011
• 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