Bladder outlet obstruction (BOO) induces structural and functional bladder changes, including elevated detrusor pressure, muscle hypertrophy, and increased matrix synthesis, leading to bladder dysfunction. Currently, no effective therapy exists for BOO-associated fibrosis and impaired detrusor contractility. We hypothesized that low-intensity extracorporeal shock wave therapy (LiESWT) could enhance detrusor contractility, urothelial proliferation, angiogenesis, and neurogenesis, thereby improving bladder function in a rat model of partial BOO (PBOO).

Male Sprague-Dawley rats were allocated into short-term (Group I) and long-term (Group II) cohorts, each subdivided into four groups: (1) sham-4 wk or sham-8 wk (sham surgery for 4 or 8 weeks), (2) PBOO-4 wk or PBOO-8 wk (PBOO via urethral ligation for 4 or 8 weeks), (3) PBOO-4 wk + SW4 or PBOO-8 wk + SW4 (PBOO for 4 or 8 weeks followed by weekly LiESWT for 4 weeks), and (4) PBOO-4 wk + SW8 or PBOO-8 wk + SW8 (PBOO for 4 or 8 weeks followed by twice-weekly LiESWT for 4 weeks). Bladder function was evaluated via voiding behavior analysis and detrusor strip contractility. Fibrosis and remodeling were assessed using Masson’s trichrome staining, while protein expression (urothelial markers, tight junctions, interstitial cells, angiogenesis, neurogenesis, TRPV channels, calcium channels, and signaling pathways including Gq/11, Gq/12, Gq/13, RhoA, RhoK, Erk1/2, p-Erk1/2, P38, p-P38, Akt, and p-Akt) was analyzed via Western blotting and immunostaining.

PBOO rats exhibited pronounced bladder dysfunction, characterized by increased micturition frequency, reduced voided volume, and diminished detrusor contractility. LiESWT ameliorated these deficits, enhancing bladder structure and function. Compared to sham controls, PBOO rats displayed wall hypertrophy, overdistension, mucosal damage, interstitial fibrosis, and altered microvascular patterns. LiESWT promoted urothelial proliferation, tight junction restoration, mucosal regeneration, interstitial cell generation, and angiogenic remodeling. In the PBOO-4 wk group, elevated muscarinic/purinergic receptors, TRPV channels, and SERCA2 correlated with overactivity, which LiESWT mitigated, alongside suppressing upregulated signaling proteins (Gq/11, Gq/12, Gq/13, RhoA, RhoK, Erk1/2, p-Erk1/2, P38, p-P38, Akt, p-Akt). Conversely, the PBOO-8 wk group showed reduced protein levels and detrusor underactivity (DU)/underactive bladder (UAB) at the decompensated stage, with LiESWT yielding limited improvement. The PBOO-4 wk group reflected detrusor overactivity (DO)/overactive bladder (OAB) at the hypertrophy/compensation stage, where LiESWT enhanced contractility.

PBOO induced significant bladder dysfunction, marked by increased micturition frequency, reduced volume, and impaired contractility. LiESWT effectively improved bladder compliance and contractile function, offering a promising therapeutic approach for PBOO-related dysfunction.