Beneficial Effect of Candesartan on Rat Diastolic Heart Failure

• Wake Ryotaro

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Kim-Mitsuyama Shokei

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences

• Izumi Yasukatsu

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Yoshida Kaoru

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Izumiya Yasuhiro

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Yukimura Tokihito

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Shiota Masayuki

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

• Yoshiyama Minoru

  Department of Medicine, Division of Cardiology, Osaka City University Graduate School of Medical Sciences

• Yoshikawa Junichi

  Department of Medicine, Division of Cardiology, Osaka City University Graduate School of Medical Sciences

• Iwao Hiroshi

  Department of Pharmacology, Osaka City University Graduate School of Medical Sciences

抄録

In this study, we examined whether an angiotensin II type 1 (AT₁)-receptor blocker improves diastolic heart failure (DHF) in Dahl salt-sensitive (DS) rats. DHF was prepared by feeding DS rats on 8% NaCl diet from 7 weeks of age. DHF was estimated with echocardiography by measuring E velocity / A velocity (E/A) of left ventricular inflow. DS rats with established DHF were orally given candesartan (1 mg/kg per day) or vehicle. After 13 days of treatment, candesartan significantly improved DHF, as shown by the reduction of E/A from 4.49 ± 1.04 to 1.98 ± 0.54 (P<0.05) and prolonged survival rate more than the vehicle. Cardiac fibrosis, apoptosis, and gene expression were estimated by Sirius Red-staining, TUNEL-staining, and Northern blot analysis, respectively. The improvement of DHF by candesartan was accompanied by the decrease in cardiac hypertrophy, fibrosis, and apoptosis, and the reduction of gene expression of brain natriuretic peptide, collagen I, and monocyte chemoattractant protein-1. Moreover, candesartan decreased cardiac inflammatory cells and reactive oxygen species, estimated by counting ED-1-positive cells and the measurement of 4-hydroxy-2-nonenal staining, respectively. These results indicate that candesartan can improve diastolic dysfunction and may slow the progression of cardiac remodelling in DS rats with established DHF.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 98 (4), 372-379, 2005

  公益社団法人 日本薬理学会

キーワード

• AT₁-receptor blocker
• diastolic heart failure
• fibrosis
• hypertrophy
• apoptosis

詳細情報

• CRID: 1390282680153198080
• NII論文ID: 10025729489
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.fp0050160
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 7402209
• PubMed: 16079469
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7402209
• Web Site: https://search.jamas.or.jp/link/ui/2006234012
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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