1Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan, (2) Department of Urology, Sapporo Central Hospital, Sapporo, Japan
Previous research demonstrated that short-term oral administration of phosphodiesterase 5 inhibitors (PDE5i) for BOO rats improved bladder contractility . However, there are few data on whether long-term oral PDE5i administration can suppress functional and morphological changes in the bladder with BOO. In this study, we evaluated the effects of tadalafil on these bladder changes using male BOO rats created by previously reported methods .
Eight weeks old male Sprague-Dawley rats were used. BOO was created by placing a polyethylene catheter around the urethra. Sham and BOO rats received oral administration of a vehicle, or tadalafil 2 mg/kg (T2) or 10 mg/kg (T10) daily after the creation of BOO. To evaluate the bladder function, we performed cystometry (CMG) and histological examination at 2, 4 and 16 weeks. The fibrosis in the smooth muscle layer was assessed by the ratio of the smooth muscle area divided by the collagen deposition area.
In the CMG measurements for BOO rats, residual volume (RV) markedly increased and the intercontraction interval (ICI) was extended in the chronic phase (16 weeks) (Figure 1a). Moreover, the detrusor fibrosis in BOO rats was significantly stronger in this phase compared with Sham rats (P <0.01). Tadalafil administration reversed the increased RV and extended ICI significantly (Figure 1b). Furthermore, the detrusor fibrosis was also significantly inhibited (P <0.01).
Long-term oral tadalafil administration can reverse histological and functional changes including underactive-like phenotype in BOO rats.