Urothelial Dysfunction, Suburothelial Inflammation and Altered Sensory Protein Expression in Men with Bladder Outlet Obstruction and Various Bladder Dysfunctions: Correlation with Urodynamics

Abstract

Purpose: We investigated urothelial integrity, suburothelial inflammation and the expression of sensory proteins in the bladder urothelium of male patients with bladder outlet obstruction and various bladder dysfunctions.

Materials and methods: We prospectively enrolled 33 men with urodynamically proven bladder outlet obstruction as the study group. Bladder biopsies were obtained from all study patients and 10 control patients. The expression of E-cadherin, zonula occludens-1, tryptase, apoptosis, TRPV (transient receptor potential vanilloid) 1 and 4, β3 adrenoreceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible/epithelial nitric oxide synthase were compared between study and control patients.

Results: Study patients had significantly lower expression of E-cadherin, and a higher number of suburothelial mast and apoptotic cells than controls. Additionally, higher expression of P2X3 and M2 muscarinic receptors, and lower expression of M3 muscarinic receptor were detected in study patients. The detrusor underactivity subgroup was characterized by significantly higher expression of β3 adrenoreceptors and lower expression of inducible nitric oxide synthase than in controls. In study patients a significantly positive correlation was noted between voided volume and E-cadherin expression (r = 0.372), volume at first sensation of filling and β3 adrenoreceptor expression (r = 0.386), and detrusor pressure and M2 muscarinic receptor expression (r = 0.496) in the bladder urothelium (each p <0.05).

Conclusions: Urothelial dysfunction, suburothelial inflammation, cellular apoptosis and alterations in sensory proteins are prominent in bladder dysfunction secondary to bladder outlet obstruction. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of bladder dysfunction and detrusor underactivity in patients with bladder outlet obstruction.

Keywords: bladder neck obstruction; inflammation; urinary bladder, neurogenic; urinary bladder, overactive; urothelium.