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

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.

• Authors: Hanna Tinel, Beatrix Stelte-Ludwig, Joachim Hütter, Peter Sandner
• Journal: BJU international (BJU Int) Vol. 98 Issue 6 Pg. 1259-63 (Dec 2006) ISSN: 1464-4096 [Print] England
• PMID: 16956354 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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