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Objectives  To investigate the influence of low‐dose sildenafil, a phosphodiesterase type 5 inhibitor ( PDE 5‐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 (30 p m ) decreased the voiding threshold pressure [to a mean ( sem ) 84.7 (3.8)% of control] and increased bladder compliance [to a mean ( sem ) 140.2 (8.3)% of control, an effect replicated in the pithed  DAPM] . Sildenafil was without effect on most voiding variables but significantly increased the number of bursts of the external urethral sphincter (EUS) per void in  DAPM  [to a mean ( sem ) 130.1 (6.9)% of control at 30 p m]  and in urethane‐anaesthetised mice [to a mean ( sem ) 117.5 (5.8)% of control at 14 ng/kg]. Sildenafil (10 and 30 p m ) increased pelvic afferent activity during both bladder filling and the isovolumetric phase [to a mean ( sem ) 205.4 (30.2)% of control at 30 p m] . Intrathecal application of sildenafil (5 μL of either 150 p m  or 1.5 n m ) did not alter cystometry and  EUS ‐ electromyography  variables in urethane‐anaesthetised mice.    Conclusions  Low‐dose sildenafil increases bladder compliance, increases pelvic nerve afferent activity, and augments the bursting activity of the EUS. 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.

bju international

Sildenafil, a phosphodiesterase type 5 inhibitor, augments sphincter bursting and bladder afferent activity to enhance storage function and voiding efficiency in mice