Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms

BJU Int. 2006 Dec;98(6):1259-63. doi: 10.1111/j.1464-410X.2006.06501.x. Epub 2006 Sep 6.

Abstract

Objective: To evaluate the potential of sildenafil, vardenafil and tadalafil, all phosphodiesterase-5 (PDE-5) inhibitors used for treating erectile dysfunction, for treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

Materials and methods: The mRNA expression of the PDE-5 was determined in rat LUT tissues. The PDE-5 inhibitors were also tested in organ-bath experiments and in a partial bladder outlet obstruction (BOO) rat model in vivo.

Results: The highest PDE-5 mRNA expression was in the bladder, followed by the urethra and prostate. PDE-5 inhibitors dose-dependently reduced the contraction of the isolated bladder, urethral and prostate strips. The rank order of potency was vardenafil > sildenafil > tadalafil. In human prostate stromal cells vardenafil inhibited cell proliferation and was more effective than tadalafil and sildenafil. In the BOO model, there was a reduction in the non-voiding contractions after bolus intravenous administration of 3 mg/kg sildenafil and vardenafil.

Conclusion: These results show that PDE-5 is expressed in LUT tissues. PDE-5 inhibitors induced significant relaxation of these tissues, inhibited the proliferation of human prostate stromal cells and reduced the irritative symptoms of BPH/LUTS in vivo. Therefore, PDE-5 inhibitors could be used as an effective treatment for BPH/LUTS.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism
  • Animals
  • Carbolines / therapeutic use
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Imidazoles / therapeutic use
  • Male
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Piperazines / therapeutic use
  • Prostatic Hyperplasia / complications
  • Prostatic Hyperplasia / drug therapy*
  • Prostatism / drug therapy*
  • Prostatism / etiology
  • Purines
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sildenafil Citrate
  • Sulfones / therapeutic use
  • Tadalafil
  • Treatment Outcome
  • Triazines / therapeutic use
  • Vardenafil Dihydrochloride

Substances

  • Carbolines
  • Imidazoles
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • RNA, Messenger
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride
  • Tadalafil
  • Sildenafil Citrate
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human
  • Pde5a protein, rat