J Korean Soc Pediatr Nephrol.  2002 Apr;6(1):85-91.

Antifibrotic Effects of Phosphodiesterase (PDE) Inhibitor in Experimental Interstitial Fibrosis induced by Unilateral Ureteral Obstruction

• Ha IS
• Um EY
• Kang HG
• Hahn HW
• Park HW
• Cheong HI
• Choi Y

Abstract

PURPOSE: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-beta1. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-beta.
MATERIALS AND METHODS
Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-beta1 in renal tissue-conditioned media was measured by ELISA.
RESULTS
Masson-trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson-trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-beta1 concentration among the groups.
CONCLUSION
A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-beta expression.

Keyword

Phosphodiesterase (PDE) inhibitor; Cilostazol; Dipyridamole; Interstitial fibrosis; Unilateral ureteral obstruction; Rat

MeSH Terms

Animals
Connective Tissue Growth Factor
Dipyridamole
Drinking Water
Enzyme-Linked Immunosorbent Assay
Fibronectins
Fibrosis*
Ligation
Rats
Rats, Sprague-Dawley
Transforming Growth Factor beta
Transforming Growth Factor beta1
Ureter*
Ureteral Obstruction*
Connective Tissue Growth Factor
Dipyridamole
Drinking Water
Fibronectins
Transforming Growth Factor beta
Transforming Growth Factor beta1