Presentation Authors: Yuh-Chen Kuo*, Hong-Chiang Chang, Ju-Ton Hsieh, Taipei, Taiwan
Introduction: Our previous study has demonstrated calcium dependent chloride channel (CaCC) involving in the pathogenesis of cyclophosphamide (CYP)-induced overactive bladder (OAB). In this study, we investigated the effect of intravesical instillation of various CaCC blockers on voiding function evaluated by continuous infusion cystometry (CMG) in CYP-induced OAB rats.
Methods: CYP-induced OAB rat was provoked by four intraperitoneal injections (CYP-OAB group: 80 mg/kg; control: saline). Continuous infusion cystometry (CMG) was performed to record the basal pressure, maximum bladder voiding pressure (MBVP), intercontraction interval (ICI) and episodes of spontaneous contraction. At the end of baseline CMG, the infused physiological saline solution was replaced by one CaCC blocker solution for 30 minutes and then was replaced again by the same reagent at a higher concentration until the maximal effect was reached. The reagents used included niflumic acid (NFA), 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), T16inh-A01 and N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid (MONNA) (N=8 for each reagent).
Results: In OAB group, the increased basal pressure was significantly ameliorated by intravesical administration of NFA (â‰¥1X10-3M), DIDS (â‰¥1X10-4M), T16inh-A01 (â‰¥1X10-5M) and MONNA (â‰¥1X10-4M) in a concentration dependent manner (Figure). The reduced MBVP was also significantly recovered by intravesical treatment of NFA (â‰¥1X10-3M), DIDS (â‰¥1X10-4M), T16inh-A01(â‰¥1X10-5M) and MONNA (â‰¥1X10-5M). The shortened ICI was significantly lengthened by intravesical infusion of NFA (â‰¥1X10-5M), DIDS (â‰¥1X10-5M), T16inh-A01 (â‰¥1X10-6M) and MONNA (â‰¥1X10-6M). The increased episodes of spontaneous contraction were significantly normalized by intravesical infusion of NFA (â‰¥1X10-2M), DIDS (â‰¥1X10-3M), T16inh-A01 (â‰¥1X10-5M) and MONNA (â‰¥1X10-5M). On the contrary, intravesical administration of CaCC blockers couldn't interfere with the CMG parameters in control group.
Conclusions: The characteristic change of CMG parameters in OAB rats could be "reversed" by intravesical administration of different CaCC blockers, showing the potential therapeutic ability of reagents acting on CaCC.