Abstract

INTRODUCTION AND OBJECTIVES: In the rat partial urethral obstruction produces bladder hypertrophy and hyperactive voiding. We previously reported that Alpha-amino-3-hydroxy-5-methyl-4isoxazolepropionate (AMPA) glutamatergic receptors are thought to participate in the control of micturition in bladder outlet obstruction (BOO) rats (AUA 2007). To determine the role of AMPA receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of chronic administration of CFM-2, a specific AMPA receptor antagonist, on the micturition reflex in conscious BOO rats. METHODS: In female Wistar rats osmotic pump ware implanted just prior to the creation of partial urethral obstruction until 4 weeks after obstruction (0.07mg/kg, or 0.70mg/kg per day). Seven days after the pump was stopped conscious filling cystometry was performed and compared with that in obstructed rats treated with vehicle. Conscious filling cystometry was also compared in sham operated rats treated CFM-2 and vehicle, respectively. RESULTS: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic CFM-2 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/ CFM-2 vs the obstructed/vehicle group chronic treatment with CFM-2 significantly increased bladder capacity and voided volume without changes in voiding efficiency or micturition pressure (Table). However, neither the frequency nor amplitude of premicturition contractions (PMCs: associated with increased activation of sensory nerve endings, resulting in urgency) was not significantly changed chronic treatment with CFM-2. In sham operated rats chronic CFM-2 treatment did not change any parameters (Table). CONCLUSIONS: The results in the current study suggest that BOO causes AMPA receptor mediated alterations in bladder afferent pathways in the rat. However, generations of PMCs have linked to other mechanisms.

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