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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalBJU International
Volume124
Issue number1
Early online date27 Feb 2019
DOIs
DateAccepted/In press - 17 Dec 2018
DateE-pub ahead of print - 27 Feb 2019
DatePublished (current) - 1 Jul 2019

Abstract

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.

Additional information

© 2019 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.

    Research areas

  • Phosphodiesterase Type 5, sildenafil, lower urinary tract, external sphincter function, mice

    Structured keywords

  • Centre for Surgical Research

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Wiley at https://doi.org/10.1111/bju.14664 . Please refer to any applicable terms of use of the publisher.

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