Benign prostatic hyperplasia (BPH)-related bladder outlet obstruction (BOO) is commonly treated by surgical relief of obstruction, but lower urinary tract symptoms (LUTS) may persist after treatment. However, the reversibility of BOO-induced bladder dysfunction and remodeling remains incompletely understood. This study aimed to evaluate functional and histological recoveries after BOO relief using a rat BOO model.

Male Sprague-Dawley rats were divided into sham, persistent BOO, and BOO-relief (BOOR) groups. Partial BOO was created by tying the urethra around an 18G metal rod and then removing the rod to produce partial urethral obstruction. In the BOOR group, the ligature knot was removed 4 weeks later to relieve the obstruction. All animals were evaluated 8 weeks after the initial surgery.
Bladder enlargement was assessed by ultrasonography. To account for variability in BOO severity, bladder weight was estimated as bladder wall volume from ultrasound data, and longitudinal changes from 4 to 8 weeks were examined in the same animals. Awake cystometry was performed to assess lower urinary tract function, including bladder capacity, maximum micturition pressure, and voiding efficiency. Histological analyses assessed smooth muscle area, collagen area, and the muscle-to-collagen ratio using Masson trichrome staining, as well as CAIX immunofluorescence to assess hypoxia-related changes.

Longitudinal, ultrasound-based estimation showed that bladder weight significantly increased from 4 to 8 weeks in the persistent BOO group, whereas it decreased after obstruction relief in the BOOR group (Figure 1A-B, both p < 0.05). Compared with the sham group, the persistent BOO group showed significantly higher maximum micturition pressure (31.46¬ ± 1.79 vs 104.2 ± 17.44 cmH2O, p < 0.05) and bladder weight (0.15¬ ± 0.04 vs 0.49 ± 0.12 g, p < 0.05), and bladder capacity (0.89¬ ± 0.39 vs 1.91 ± 0.66 mL, p < 0.05), as well as a significant decrease in voiding efficiency (96.71¬ ± 4.38 vs 29.68 ± 10.24%, p < 0.05) (Figure 1C).  Compared with the persistent BOO group, the BOOR group showed significantly lower maximum micturition pressure (104.2 ± 17.44 vs 38.29 ± 2.91 cmH2O, p < 0.05), improved voiding efficiency (29.68 ± 10.24 vs 84.89 ± 13.62%, p < 0.05), reduced bladder weight (0.49 ± 0.12 vs 0.23 ± 0.01 g, p < 0.05), and lower bladder capacity (1.91 ± 0.66 vs 0.78 ± 0.25 mL, p < 0.05), approaching sham levels (Figure 1D). However, histological recovery was incomplete. Masson trichrome staining showed a significant recovery of muscle area after obstruction relief (p < 0.05), whereas collagen area did not show significant improvement (Figure 2A-B). The muscle-to-collagen ratio was significantly lower in BOOR vs. persistent BOO groups (p < 0.05). CAIX staining further suggested persistent hypoxia-related changes in the BOOR bladder (Figure 2C-D).

The longitudinal change in estimated bladder weights suggests that bladder remodeling progresses between 4 and 8 weeks after BOO. Obstruction relief at 4 weeks appears not only to stop this progression but also to partially reverse the remodeling. Relief of obstruction improved several functional parameters, including maximum micturition pressure and voiding efficiency, and reduced the compensatory increase in bladder capacity. However, histological abnormalities were not fully reversed. The decrease in the muscle-to-collagen ratio after obstruction relief suggests a reduction in compensatory muscle hypertrophy, whereas persistent collagen- and hypoxia-related changes indicate residual structural remodeling. These findings suggest that functional improvement following BOO relief does not necessarily indicate full reversal of bladder remodeling.

Obstruction relief at 4 weeks partially reversed bladder remodeling and improved lower urinary tract function, but histological abnormalities remained. Residual bladder changes such as fibrosis and ischemia after BOO relief may represent a therapeutic target for post-surgical LUTS in BPH patients.