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.

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

“…The same study demonstrated inhibition of human prostate stromal cell proliferation with vardenafil in vivo. 23 Tinel et al 24 utilized a rat model that demonstrated a PDE-inhibitor dosedependent reduction in smooth muscle contraction of bladder, urethral and prostate strips. A reduction in bladder nonvoiding contractions was noted in the rat BOO model after administration of sildenafil and vardenafil.…”

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

“…If cAMP-dependent signaling is favored in the presence of a α1-blocker, this could increase cGMP levels initially stimulated by tadalafil, which had until then remained functionally silent. Such positive cross-talk mechanism between cGMP and cAMP signaling previously described in other systems, could be the origin of the enhanced relaxant effect of the combination (20)(21)(22)(23).…”

PDE5 inhibitors for LUTS

“…93 Experimental models, in human and rat tissue, have shown that PDE5 inhibitors decrease nonvoiding bladder contractions. 94,83 In addition, PDE5 inhibitors have been shown to improve urodynamic parameters in SCI patients. 82 PDE5 inhibitors offer an opportunity to treat ED and LUTS concurrently.…”