Presence of Phosphodiesterase Type 5 in the Spinal Cord and its Involvement in Bladder Outflow Obstruction Related Bladder Overactivity

Füllhase, Claudius; Hennenberg, Martin; Giese, Armin; Schmidt, Michael; Strittmatter, Frank; Soler, Roberto; Gratzke, Christian; Andersson, Karl‐Erik; Stief, Christian G.

doi:10.1016/j.juro.2013.03.112

Cited by 14 publications

(9 citation statements)

References 29 publications

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“…Several previous studies have reported that PDE5‐Is and NO reduce mechanosensitive afferent activity of both A δ‐ and C‐fibres evoked by bladder distension in the rat . However, it is worth noting that these reports of inhibitory effects of PDE5‐Is on bladder afferent discharge were found at higher bladder pressures (30 cmH 2 O) than the voiding threshold in normal rats (about 10–15 cmH 2 O ) possibly reflecting inhibitory effects in a noxious range (i.e., on nociceptors), rather than in the normal range of storage and threshold pressures. This increase in the afferent activity may account for the reduction in the threshold pressure for voiding produced by sildenafil.…”

Section: Discussionmentioning

confidence: 86%

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

et al. 2019

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Objectives To investigate the influence of low‐dose sildenafil, a phosphodiesterase type 5 inhibitor (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 (30 pm) 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 pm] and in urethane‐anaesthetised mice [to a mean (sem) 117.5 (5.8)% of control at 14 ng/kg]. Sildenafil (10 and 30 pm) increased pelvic afferent activity during both bladder filling and the isovolumetric phase [to a mean (sem) 205.4 (30.2)% of control at 30 pm]. Intrathecal application of sildenafil (5 μL of either 150 pm or 1.5 nm) 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.

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Section: Discussionmentioning

confidence: 86%

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

et al. 2019

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“…Therefore, this enzyme may have significant effect on the pathogenesis of BPH-LUTS. In addition, there is information stating that PDE5 expression in the spinal cord area is responsible for urination control [14]. Tadalafil administration appeared to increase the amount of cyclic nucleotides in the urinary bladder, prostate and cavernous bodies of penis.…”

Section: Methodsmentioning

confidence: 99%

Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors

Колонтарев

Govorov

Kasyan

et al. 2016

CEJU

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IntroductionBenign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors.Material and methodsThe authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed.ResultsTwenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected.ConclusionsThe current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

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“…PDE5 is present in the tissue and vasculature of the bladder neck, prostatic urethra, prostate, and corpus cavernosum14,15 and is implicated in the pathology of LUTS/ED 10,16. Furthermore, PDE5 was found to be expressed in the sacral spinal regions and micturition control areas 17. In an animal model of bladder hyperactivity secondary to bladder outlet obstruction, the administration of sildenafil helped alleviate bladder overactivity when administered intravenously and intrathecally, indicating possible neurologic involvement of this class of medications 17.…”

Section: Tadalafilmentioning

confidence: 99%

“…Furthermore, PDE5 was found to be expressed in the sacral spinal regions and micturition control areas 17. In an animal model of bladder hyperactivity secondary to bladder outlet obstruction, the administration of sildenafil helped alleviate bladder overactivity when administered intravenously and intrathecally, indicating possible neurologic involvement of this class of medications 17. In transurethral resection of the prostate specimens, cGMP and cAMP (cyclic adenosine monophosphate) were significantly higher in patients receiving tadalafil or udenafil than in the control group 18.…”

Section: Tadalafilmentioning

confidence: 99%

Management options for the treatment of benign prostatic hyperplasia with or without erectile dysfunction: a focus on tadalafil and patient considerations

Alsaikhan¹,

Alrabeeah²,

Carrier³

2014

IJGM

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Lower urinary tract symptoms (LUTS) and erectile dysfunction increase with age. Several studies have identified a true association between these two disorders. Basic research studies have shown a significant decrease in the nitric oxide/cyclic guanosine monophosphate pathway with age that leads to decreased relaxation of the bladder wall and prostate and worsening LUTS. In this review article, we will focus on the potential use and clinical significance of phosphodiesterase-5 inhibitors in the treatment of LUTS secondary to benign prostate hyperplasia.

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Presence of Phosphodiesterase Type 5 in the Spinal Cord and its Involvement in Bladder Outflow Obstruction Related Bladder Overactivity

Abstract: Phosphodiesterase type 5 is expressed in the rat spinal cord. Intravenous sildenafil may exert part of its urodynamic effect in rats with partial urethral obstruction/bladder overactivity via an effect on the sacral spinal cord.

Cited by 14 publications

References 29 publications

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

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

Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors

Management options for the treatment of benign prostatic hyperplasia with or without erectile dysfunction: a focus on tadalafil and patient considerations

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