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Heart and Vessels

, Volume 16, Issue 6, pp 249–256 | Cite as

Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure

  • Koki Takahashi
  • Tomohiro Osanai
  • Takao Nakano
  • Makoto Wakui
  • K. Okumura
ORIGINAL ARTICLE

Abstract.

Phosphodiesterase (PDE) was shown to be downregulated in the failing hearts of transplant recipients, while it was upregulated in hypertrophied hearts induced by isoproterenol and calsequesterin overexpression. We examined the time course of gene expression and the activity of PDE3 and PDE4 in an animal model of salt-induced hypertension, left ventricular hypertrophy, and congestive heart failure (CHF). Dahl salt-sensitive (DS, n = 25) and salt-resistant rats (DR, n = 25) were fed with an 8% NaCl diet after the age of 6 weeks. At 11 weeks (hypertension and hypertrophy stage in DS), PDE4 activity in the heart was higher in DS than in DR. At 18 weeks (hypertension and CHF stage in DS), both PDE3 and PDE4 activity in both the heart and aorta was approximately twofold higher in DS than in DR. The ratios of PDE3 and PDE4 mRNA to GAPDH mRNA in the heart were both approximately twofold higher in DS than in DR at 11 and 18 weeks. The cardiac cyclic adenosine monophosphate content and plasma nitric oxide concentration were higher in DS than in DR at 11 weeks but both of them were lower in DS than in DR at 18 weeks of age. In this animal model, gene expressions of PDE3 and PDE4 were augmented from the hypertrophic stage. PDE3 and PDE4 activities were subsequently enhanced in the CHF stage and seemed to contribute to the development and exacerbation of CHF.

Key words Phosphodiesterase Hypertension Heart failure Nitric oxide Cyclic adenosine monophosphate 

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Copyright information

© Springer-Verlag Tokyo 2002

Authors and Affiliations

  • Koki Takahashi
    • 1
  • Tomohiro Osanai
    • 1
  • Takao Nakano
    • 1
  • Makoto Wakui
    • 2
  • K. Okumura
    • 1
  1. 1.Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. okumura@cc.hirosaki-u.ac.jpJP
  2. 2.Department of Physiology, Hirosaki University School of Medicine, Hirosaki, JapanJP

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