Fig. 1.

Intravesical infusion of the transient receptor potential vanilloid family member 4 (TRPV4) antagonist HC-067047 reduces voiding frequency and nonvoiding contractions (NVCs) in transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE), as demonstrated using continuous-fill, open-outlet, conscious cystometry. A and B: representative bladder function recordings from the same NGF-OE mouse before and after intravesical instillation of the TRPV4 antagonist HC-067047 (1 µM). A1 and A2: before HC-067047 instillation, NGF-OE mice exhibited increased voiding frequency and an increased number of NVCs during the filling phase (arrows). B1 and B2: after HC-067047 instillation, NGF-OE mice exhibited a reduction in voiding frequency [i.e., increased duration of intercontraction interval (ICI) and increased infused volume (IV) before micturition event]. BP, bladder pressure. C–E: summary histograms of void volume (VV), ICI, and NVCs measured from bladder function testing by conscious cystometry in wild-type (WT) and NGF-OE mice before and after intravesical instillation of HC-067047 (1 µM). NGF-OE mice exhibited significantly (*P ≤ 0.01) reduced VV (C) and ICI (D) compared with littermate WT mice. Intravesical instillation of HC-067047 (1 µM) significantly (*P ≤ 0.01) increased VV (C) and ICI (D) in NGF-OE and littermate WT mice. NGF-OE mice exhibited a significantly (*P ≤ 0.01) greater number of NVCs per voiding cycle than littermate WT mice (E). Intravesical infusion of HC-067047 (1 µM) significantly (*P ≤ 0.01) reduced the number of NVCs during the filling phase of the cycle compared with vehicle-treated NGF-OE mice (E). The number of NVCs was still significantly (*P ≤ 0.01) greater in NGF-OE mice treated with HC-067047 than in littermate WT mice treated with HC-067047 (E). Intravesical infusion of HC-067047 was without effect in littermate WT mice (E). Values are means ± SE; n = 8 for each group.