Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast.

PURPOSE: To prove that phosphodiesterase type-4 inhibitors could potentially treat obesity-associated overactive bladder through modulation of the systemic inflammatory response.

METHODS: In this 12-week study, 90 female Sprague-Dawley rats were divided into three groups: (1) vehicle-treated normal diet (ND)-fed rats; (2) vehicle-treated high-fat diet (HFD)-fed rats; and (3) roflumilast-treated HFD-fed rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of HFD feeding in the test group. At 12 weeks, a urodynamic study was performed in ten rats of each group. Bladder tissue was extracted, the bladder mucosa was separated under microscopy, and bladder detrusor smooth muscle (DSM) expression of TNF-α, interleukin (IL)-6, IL-1β, and nuclear factor kappa B (NF-κB) were analyzed using Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTS: Bodyweights of the HFD-fed rats significantly increased and were not ameliorated by roflumilast treatment. Cystometry evidenced augmented frequency and non-void contractions in obese rats that were also prevented by roflumilast. These alterations were accompanied by a markedly increased expression of TNF-α, IL-6, IL-1β, and NF-κB in DSM of obese rats. Furthermore, roflumilast decreased expression of inflammatory factors in DSM.

CONCLUSIONS: Oral treatment with roflumilast in rats fed an HFD restores normal bladder function and downregulates expression of inflammatory factors in the bladder.