Effects of the Selective Prostacyclin Receptor Antagonist RO3244019 on the Micturition Reflex in Rats

Purpose: We investigated the role of prostacyclin on afferent modulation of the micturition reflex using the novel selective prostacyclin receptor antagonist RO3244019 in rat models of bladder function.Materials and Methods: The effects of RO3244019 on urodynamic parameters were evaluated in 3 rat models. In the anesthetized isovolumetric bladder contraction and the volume induced micturition reflex (Refill) models the effects of RO3244019 and chronic capsaicin desensitization were compared. In the citric acid induced detrusor overactivity model the effects of RO3244019 and the cyclooxygenase inhibitor indomethacin were evaluated.Results: In the isovolumetric bladder contraction model RO3244019 dose dependently decreased bladder contraction frequency with a mean ± SEM maximum decrease of 72.2% ± 4.3% at 3.16 mg/kg. RO3244019 also dose dependently increased the micturition threshold in the Refill model with a maximum increase of 86.9% ± 19.1% at 3.0 mg/kg. In animals that were chronically treated with caps...