Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure

Masako Saka, Koji Obata, Sahoko Ichihara, Xian Wu Cheng, Hirotaka Kimata, Takao Nishizawa, Akiko Noda, Hideo Izawa, Kohzo Nagata, Toyoaki Murohara, Mitsuhiro Yokota

研究成果: Article査読

44 被引用数 (Scopus)

抄録

Statin therapy may be associated with lower mortality in patients with heart failure, but the underlying mechanism of such an association is unknown. We have evaluated the effects of pitavastatin on cardiac function and survival in a rat model of hypertensive heart failure and investigated the molecular mechanism of the observed effects. Dahl salt-sensitive rats fed with high-salt diet from 7 weeks of age developed compensatory left ventricular hypertrophy at 12 weeks and heart failure at 19 weeks. Dahl salt-sensitive rats were treated with either vehicle or pitavastatin (0.3 mg/kg per day) from 7 or 12 weeks. Both early-onset and late-onset pitavastatin treatment reduced left ventricular fibrosis, improved cardiac function, and increased the survival rate apparent at 19 weeks. The increases in the expression levels of hypertrophic, profibrotic, and metalloproteinase genes as well as in gelatinase activities in the heart induced by the high-salt diet were suppressed by pitavastatin treatment. Furthermore, the level of cardiac endothelin-1 was increased in association with the development of heart failure in a manner sensitive to treatment with pitavastatin. Both early and late pitavastatin treatment thus improved cardiac function and survival, with modulation of extracellular matrix remodeling and endothelin-1 signaling possibly contributing to these beneficial effects.

本文言語English
ページ(範囲)770-779
ページ数10
ジャーナルJournal of Cardiovascular Pharmacology
47
6
DOI
出版ステータスPublished - 06-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 循環器および心血管医学

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