Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension

M. Shimoyama, D. Hayashi, Y. Zou, E. Takimoto, M. Mizukami, K. Monzen, Y. Yazaki, R. Nagai, I. Komuro

Research output: Contribution to journalArticle

Abstract

BACKGROUND: It remains unclear how hemodynamic overload induces cardiac hypertrophy. Recently, activation of calcium-dependent phosphatase, calcineurin, has been elucidated to induce cardiac hypertrophy. In the present study, we examined the role of calcineurin in load-induced cardiac hypertrophy by using Dahl salt-sensitive (DS) rats, which develop both pressure and volume overload when fed a high salt diet. METHODS AND RESULTS: In the DS rat heart, the activity of calcineurin was increased and cardiac hypertrophy was induced by high salt diet. Treatment of DS rats with the calcineurin inhibitor FK506 (0.1 or 0.01 mg/kg every second day) from the age of 6 weeks to 12 weeks inhibited the activation of calcineurin in the heart in a dose-dependent manner and attenuated the development of load-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Additionally, treatment with 0.1 mg/kg every second day but not with 0.01 mg/kg every second day of FK506 from the age of 12 weeks to 16 weeks induced regression of cardiac hypertrophy in DS rats. Load-induced reprogramming of gene expression was also suppressed by the FK506 treatment. CONCLUSIONS: These results suggest that calcineurin is involved in the development of cardiac hypertrophy in rats with salt-sensitive hypertension and that inhibition of calcineurin could induce regression of cardiac hypertrophy.

Original languageEnglish (US)
Pages (from-to)114-118
Number of pages5
JournalJournal of Cardiology
Volume37
Issue number2
StatePublished - Feb 2001
Externally publishedYes

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Cardiomegaly
Salts
Calcineurin
Inbred Dahl Rats
Hypertension
Tacrolimus
Hemodynamics
Diet
Calcineurin Inhibitors
Fibrosis
Calcium
Gene Expression
Pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Shimoyama, M., Hayashi, D., Zou, Y., Takimoto, E., Mizukami, M., Monzen, K., ... Komuro, I. (2001). Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. Journal of Cardiology, 37(2), 114-118.

Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. / Shimoyama, M.; Hayashi, D.; Zou, Y.; Takimoto, E.; Mizukami, M.; Monzen, K.; Yazaki, Y.; Nagai, R.; Komuro, I.

In: Journal of Cardiology, Vol. 37, No. 2, 02.2001, p. 114-118.

Research output: Contribution to journalArticle

Shimoyama, M, Hayashi, D, Zou, Y, Takimoto, E, Mizukami, M, Monzen, K, Yazaki, Y, Nagai, R & Komuro, I 2001, 'Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension', Journal of Cardiology, vol. 37, no. 2, pp. 114-118.
Shimoyama, M. ; Hayashi, D. ; Zou, Y. ; Takimoto, E. ; Mizukami, M. ; Monzen, K. ; Yazaki, Y. ; Nagai, R. ; Komuro, I. / Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. In: Journal of Cardiology. 2001 ; Vol. 37, No. 2. pp. 114-118.
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