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

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Abstract

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.

Original languageEnglish
Pages (from-to)770-779
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume47
Issue number6
DOIs
Publication statusPublished - 01-06-2006

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Endothelins
Heart Failure
Survival
Inbred Dahl Rats
Endothelin-1
Salts
Diet
Therapeutics
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Gelatinases
Left Ventricular Hypertrophy
Metalloproteases
Extracellular Matrix
pitavastatin
Fibrosis
Survival Rate
Mortality
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Saka, Masako ; Obata, Koji ; Ichihara, Sahoko ; Cheng, Xian Wu ; Kimata, Hirotaka ; Nishizawa, Takao ; Noda, Akiko ; Izawa, Hideo ; Nagata, Kohzo ; Murohara, Toyoaki ; Yokota, Mitsuhiro. / Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. In: Journal of Cardiovascular Pharmacology. 2006 ; Vol. 47, No. 6. pp. 770-779.
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Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. / Saka, Masako; Obata, Koji; Ichihara, Sahoko; Cheng, Xian Wu; Kimata, Hirotaka; Nishizawa, Takao; Noda, Akiko; Izawa, Hideo; Nagata, Kohzo; Murohara, Toyoaki; Yokota, Mitsuhiro.

In: Journal of Cardiovascular Pharmacology, Vol. 47, No. 6, 01.06.2006, p. 770-779.

Research output: Contribution to journalArticle

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