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

• Published in: PloS one 2019-08, Vol.14 (8), p.e0220788-e0220788
• Main Authors: Balog, Brian M, Tangada, Abhilasha, Sheth, Pooja, Song, Qi-Xiang, Couri, Bruna M, Porras, Leah L, Deng, Gary G, Damaser, Margot S
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Biomedical engineering; Bladder; Complications and side effects; Contraction; Disruption; Dosage and administration; Drug therapy; Drug Therapy, Combination; Engineering; Engineering and Technology; Female; Fibrosis; Fuel consumption; Histology; Inhibitors; Laboratories; Medicine and Health Sciences; Mirabegron; Muscle Contraction - drug effects; Muscles; Phosphodiesterase; Phosphodiesterase 4 Inhibitors - therapeutic use; Phosphodiesterase 5 Inhibitors - therapeutic use; Rats, Sprague-Dawley; Rodents; Roflumilast; Side effects; Smooth muscle; Statistical analysis; Stokes, Louis; Tadalafil; Urinary Bladder - drug effects; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - physiopathology; Urinary incontinence; Urination - drug effects; Urogenital system; Urology; Variance analysis; Veterans
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220788

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. 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