Sildenafil, a Phosphodiesterase Type 5 Inhibitor, augments sphincter bursting and bladder afferent activity to enhance storage function and voiding efficiency in mice

OBJECTIVES: To investigate the influence of low dose phosphodiesterase type 5 inhibitors (PDE5-I) on the function of the mouse lower urinary tract (LUT).

MATERIALS AND METHODS: Adult male mice were decerebrated and arterially-perfused with a carbogenated Ringer's solution to establish the decerebrate arterially-perfused mouse (DAPM). To allow distinction between central neural and peripheral actions of sildenafil, experiments were conducted in both the DAPM and in a 'pithed' DAPM which has no functional brainstem or spinal cord. The action of systemic and intrathecal sildenafil on micturition was assessed in urethane-anaesthetised mice.

RESULTS: In the DAPM, systemic perfusion of sildenafil (30pM) decreased the voiding threshold pressure (to 84.7 ± 3.8% of control) and increased bladder compliance (to 140.2 ± 8.3% of control, an effect replicated in the pithed DAPM). Sildenafil was without effect on most voiding parameters but significantly increased the number of bursts of external urethral sphincter per void in DAPM (to 130.1 ± 6.9% of control at 30pM) and in urethane-anaesthetised mice (to 117.5 ± 5.8% of control at 14ng/kg). Sildenafil (10 and 30 pM) increased pelvic afferent activity during both bladder filling and the isovolumetric phase (to 205.4 ± 30.2% of control at 30pM). Intrathecal application of sildenafil (5μl of either 150pM or 1.5nM) did not alter cystometry and EUS-EMG parameters in urethane-anaesthetised mice.

CONCLUSIONS: Low dose sildenafil increases bladder compliance, increases pelvic nerve afferent activity and augments the bursting activity of the external urethral sphincter. We propose that the novel actions on afferent traffic and sphincter control may contribute to its beneficial actions to restore storage and voiding efficiency in LUT dysfunction. This article is protected by copyright. All rights reserved.