The effect of phosphodiesterase isoenzyme 5 inhibitors on ureteropelvic junction obstruction in rabbits

Urol Int. 2009;83(3):316-22. doi: 10.1159/000241675. Epub 2009 Oct 13.

Abstract

Objective: To determine the effects of phosphodiesterase isoenzyme 5 (PDE5) inhibitors upon ureteropelvic junction obstruction (UPJO) in rabbits.

Materials and methods: Twenty-four New Zealand rabbits were randomly divided into three groups: sham-operated animals (group A; right-sided operations comprised subgroup A1 and left-sided operations comprised subgroup A2), operated animals (group B) and operated animals that received vardenafil (group C). The right-sided junctions of group A (A1) were not exposed, and therefore made up the control group. The UPJO model was established by partial obstruction of the left junction. Intravenous pyelograms were performed before and after the operation. HE staining and microscopic examinations were performed to chart the pathological changes. Immunohistochemistry (streptavidin peroxidase) was used to test the expression of TGF-beta1 and nNOS in the junctions. RT-PCR detected mRNA expression of TGF-beta1.

Results: We observed serious hydronephrosis in group B and moderate hydronephrosis in group C, but not in group A. We also observed large pathological changes in group B, but little change in group C and no change in subgroups A1 and A2. The level of TGF-beta1 in group B was significantly higher than in groups A and C; group C expressed more TGF-beta1 than group A. More nNOS was detected in group C than group B, although the two groups both expressed nNOS at lower levels than group A.

Conclusions: More TGF-beta1 and less nNOS are expressed when the junction is obstructed. PDE5 inhibitors may be able to regulate these 2 factors, or other factors that have not been discussed in this experiment, in order to halt the progression of UPJO.

MeSH terms

  • Animals
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Isoenzymes
  • Kidney Pelvis*
  • Phosphodiesterase 5 Inhibitors*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Rabbits
  • Sulfones / pharmacology
  • Sulfones / therapeutic use
  • Triazines / pharmacology
  • Triazines / therapeutic use
  • Ureteral Obstruction / drug therapy*
  • Ureteral Obstruction / metabolism
  • Vardenafil Dihydrochloride

Substances

  • Imidazoles
  • Isoenzymes
  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride