AB259. TRPV1 receptor associated with detrusor overactivity induced by partial bladder outlet obstruction in rats

BACKGROUND: To investigate the role of TRPV1 in the pathological process of DO induced by partial bladder outlet obstruction (pBOO). METHODS: In 40 female Wistar rats, pBOO was achieved by partial urethral ligation and urodynamic analysis was taken to filter the DO rats six weeks later. Urinary bladder and dorsal root ganglia (DRG) were removed and RT-PCR, Western Blot and IHC were performed to investigate the expression and location of TRPV1 in control and DO rats. Effect of different concentrations of TRPV1 agonist, as well as TRPV1 antagonist, was also evaluated with isolated detrusor strips. RESULTS: Forty female Wistar rats received pBOO surgery and 24 of them developed DO. Expression of TRPV1 mRNA and protein in urinary bladder and dorsal root ganglia (DRG) significantly increased in pBOO induced OAB rats. While that did not significantly change after de-urothelial treatment both in OAB and control rats. Immunohistochemistry observed linear TRPV1-reactive staining mainly in suburothlial and muscular layer. In isolated detrusor strips studies, the amplitude and frequency of contractions of DO tissues were significantly higher than that of control ones (P<0.05). Capsaicin significantly increased the amplitude but not frequency of detrusor intrinsic contractility and this effect was enhanced in OAB conditions. All changes induced by capsaicin were blocked by capsazepine pre-incubated. CONCLUSIONS: In pBOO induced DO rats, over-expressed TRPV1 was involved in DO pathological process by directly sensitizing bladder afferent fibers or indirectly enhancing detrusor intrinsic properties.