Combination phosphodiesterase type 4 inhibitor and phosphodiesterase type 5 inhibitor treatment reduces non-voiding contraction in a rat model of overactive bladder

Abstract

Introduction Current treatments for overactive bladder (OAB) are often discontinued due to side effects or lack of efficacy. The goal of this study was to determine if combining a phosphodiesterase type 4 inhibitor (PDE4i); with a type 5 inhibitor (PDE5i); would have a beneficial effect on OAB symptoms and if a reduced dose of PDE4i in combination with PDE5i could also provide a beneficial effect in OAB. We hypothesized that PDE5i and PDE4i combination treatment could be utilized to reduce non-voiding contractions and smooth muscle disruption in a rat model of OAB. Methods Fifty-eight age-matched Sprague-Dawley rats underwent PBOO and daily gavage with PDE4i alone (roflumilast; 1mg/kg), PDE5i alone (tadalafil;10mg/kg), high dose combination (PDE4i 1mg/kg, PDE5i 10mg/kg), low dose combination (PDE4i 0.2mg/kg, PDE5i 10mg/kg), or vehicle for 28 days. Fourteen animals underwent sham PBOO with vehicle. Rats underwent conscious and anesthetized cystometry 28 days after PBOO and were euthanized for qualitative bladder histology. One-way ANOVA on ranks with a Dunn’s post hoc test was used to indicate statistically significant differences between groups (p<0.05). Results Bladder & urethral weight was significantly increased after PBOO with vehicle, PDE4i alone, and PDE5i alone, but not with either combination treatment. Frequency of non-voiding contractions during both conscious and anesthetized cystometry increased significantly after PBOO with vehicle, but not after PDE4i or high dose combination treatments compared to sham PBOO. Threshold pressure for voiding was significantly decreased with high dose combination compared to vehicle. PBOO treated with PDE4i alone or high dose combination showed less bladder smooth muscle fibrosis than vehicle, PDE5i alone, or low dose combination treatments. Conclusion A PDE4i and PDE5i combination treatment has potential benefit in reducing OAB symptoms, but future research is needed.

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia

“…Nonvoiding contraction (NVC) parameters, namely the number, mean amplitude, and maximum amplitude, were recorded and analyzed. NVCs were characterized by an increase in pressure of >20% from baseline, defined as the bladder pressure immediately prior to the NVC; this was observed as an increase in pressure that did not result in void [59].…”

Adipose-derived stem cell-derived microvesicles prevent progression to bladder underactivity secondary to long-termed bilateral partial iliac arterial occlusion-induced bladder ischemia

“…Non-voiding contractions (NVCs) were characterized by an increase in pressure of > 20% from baseline, de ned as the bladder pressure immediately before voiding. This was observed as an increase in pressure, which did not result in voids [20]. The number, mean amplitude, and maximum amplitude were analyzed.…”