Relaxation Effect of Phosphodiesterase-5 Inhibitor on the Animal Bladder and Prostatic Urethra: in vitro and in vivo Study

Abstract

Aim: To assess the relaxation effect of the phosphodiesterase-5 inhibitor udenafil on the bladder and prostatic urethra and its therapeutic potentials for benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Methods: For the in vitro study, muscle strips from urinary bladder and urethra were prepared from male New Zealand rabbits. The strips were mounted in organ baths and connected to force transducers. After stabilization, maximal tissue contractions were obtained by the addition of phenylepinephrine for urethra strips and carbachol for bladder strips. When the contraction was stabilized, a dose-response curve of udenafil was constructed. For the in vivo study using adult male Sprague-Dawley rats, changes of intravesical pressure and urethral perfusion pressure after intraarterial administration of udenafil were monitored. Results: Udenafil significantly relaxed the bladder and urethra strips in a dose-dependent manner. At 10^–3 M, udenafil induced a significant relaxation of the bladder strips by 37.3% and of the urethra strips by 44.0%. In the in vivo study, the intercontraction interval was significantly prolonged (p < 0.01) and the duration of urethral relaxation with high-frequency oscillations was significantly prolonged (p < 0.01) after udenafil. Conclusions: Udenafil had relaxant effects on the bladder and prostatic urethral smooth muscle. Clinically, udenafil could be applied as an effective treatment for BPH/LUTS.

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model

“…[24] The authors showed lesser number of papillary projections, and acini in the finasteride group than control and doxazosin groups. [5] We determined less number of papillary projections per acini in sildenafil citrate group than the others without significant intergroup difference.…”

“…Erectile dysfunction (ED) is another common disorder and is often seen with BPH and LUTS. [5] Mulhall et al [9] reported that PDE-5 inhibitors improve not only symptoms of ED but also LUTS with relaxation of lower urinary tract tissues.…”

“…[14,15] Cyclic adenosine monophosphate is more important than cGMP for detrusor function, hence the cAMP pathway in the bladder has been more thoroughly investigated than cGMP. Five isoforms of PDEs (1)(2)(3)(4)(5) were isolated and demonstrated in human and porcine detrusor in functional studies. [16,17] The effect of vardenafil on cyclic nucleotide levels and bladder contraction was investigated in rat detrusor by Werkstrom et al [18] Relexation was accompanied with increased levels of both cAMP and cGMP, and it was proposed that vardenafil-induced relaxation of rat detrusor was mediated by cAMP through inhibition of cGMP dependent cAMP-PDE.…”

“…PDE-5 inhibitors dose dependently decrease the contractions of prostate and bladder. [5] Mechanism of PDE-5 is supposedly mediated via cyclic guanosine monophosphate (cGMP), smooth muscle relaxation in response to nitric oxide. Bladder, urethra and prostate tissues have highest PDE-5 mRNA expressions in rat urinary tracts.…”

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic evaluation and action of sildenafil citrate

“…However, the involvement of changes in the production and efficacy of NO in urethral dysfunction due to diabetes has been little documented in the literature. These recently studies demonstrated the impact of sildenafil on micturition behavior and urethral tone, and that irrespective of the hormonal status, sildenafil decreased leak point pressure by a nNOS-mediated mechanism [15][16][17] .…”