Relaxant Effects of Sildenafil on the Human Isolated Bladder Neck

Bittencourt, J. A.; Tano, T.; Gajar, Sessin A.; Resende, Ângela Castro; Neto, Miguel de Lemos; Damião, Ronaldo; Criddle, David N.; de, Graziele Freitas; Moura, Roberto Soares de

doi:10.1016/j.urology.2008.06.060

Cited by 28 publications

(14 citation statements)

References 26 publications

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“…In support of this theory, NOS activity has been demonstrated in tissue from human urethra, corpus cavernosum, prostate, vas deferens and bladder neck (22). In addition, a relaxing effect of NO donors and phosphodiesterase‐5 (PDE5) inhibitors on human prostate tissue and bladder neck has been shown (23–26). In vitro models have also shown an antiproliferative effect of NO donors on prostatic smooth muscle cells (27).…”

Section: Pathophysiological Mechanisms For Bph/luts‐associated Sexualmentioning

confidence: 99%

Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events

Mirone

Sessa²,

Giuliano

et al. 2011

International Journal of Clinical Practice

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Benign prostatic hyperplasia (BPH) is a common disease in older men that can lead to lower urinary tract symptoms (LUTS). Male sexual dysfunction is also an age-related condition. Epidemiological studies have confirmed an association between BPH/LUTS and sexual dysfunction in ageing men that is independent of the effects of age, other co-morbidities and lifestyle factors. Proposed pathophysiological mechanisms for BPH/LUTS-associated sexual dysfunction include the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway, rho-kinase and endothelin-1 activity, autonomic nervous system overactivity and the metabolic syndrome, and pelvic organ atherosclerosis. Both BPH/LUTS and sexual dysfunction can have a substantial negative impact on a man's quality of life. However, urologists and primary care physicians appear to under-recognise sexual dysfunction in men with BPH/LUTS. Current guidelines recommend alpha-blockers and 5-alpha reductase inhibitors, either alone or in combination, among appropriate medical treatment options for BPH/LUTS. Randomised, controlled trials demonstrate that these therapies can be associated with sexual adverse effects (AEs) such as loss of libido, erectile dysfunction and ejaculatory disorders. Sexual dysfunction should be fully evaluated in men requiring treatment for BPH/LUTS using validated questionnaires. Management of sexual dysfunction in men treated for BPH/LUTS should involve assessment of co-morbidities and concomitant medications, consideration of lifestyle interventions such as weight loss and increased physical activity to improve risk factors and, if necessary, introduction of pharmacotherapies. In addition, physicians should provide patients with proper counselling on the possible sexual AEs of medical therapies for BPH/LUTS and their impact on sexual satisfaction, while being aware of the possibility that counselling in itself is likely to influence reported rates of sexual dysfunction.

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Section: Pathophysiological Mechanisms For Bph/luts‐associated Sexualmentioning

confidence: 99%

Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events

Mirone

Sessa²,

Giuliano

et al. 2011

International Journal of Clinical Practice

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“…5,6,14,15 In addition, there is strong evidence demonstrating that PDE5i affect and improve LUTS. 16 Moreover, an association between LUTS and erectile dysfunction has been clearly established, and recently reviewed by Mouli and McVary. 17 Gacci and colleagues reported a small three-armed study that was similar to ours, using daily vardenafil, on-demand vardenafil, and a placebo group.…”

Section: Discussionmentioning

confidence: 98%

“…18 Pertinently, Bittencourt and colleagues recently demonstrated that sildenafil relaxes human bladder tissue depending on the nitric oxide/cGMP pathway. 16 It is possible that relaxation of bladder neck tissue facilitated by sildenafil hyndman et al…”

Section: Discussionmentioning

confidence: 99%

Nightly sildenafil use after radical prostatectomy has adverse effects on urinary convalescence: Results from a randomized trial of nightly vs on-demand dosing regimens

Hyndman

Bivalacqua

Mettee

et al. 2015

CUAJ

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Introduction: This is a report on potency results from a randomized trial of nightly versus on-demand sildenafil after nerve-sparing radical prostatectomy (RP). A secondary objective was to analyze the effects of these sildenafil administration schemes on urinary health-related quality of life after RP. Methods: In total, 100 potent men were equally randomized to nightly and on-demand sildenafil 50 mg after minimally-invasive RP for 1 year. Health-related quality of life questionnaires were administered at various postoperative intervals. Urinary function was assessed using appropriate expanded prostate cancer index composite (EPIC) subscales. Analyses of covariance and linear mixed-effects modeling were used to compare the effects of treatment over time on urinary recovery, controlling for age, nervesparing score, and time from surgery. Results: The nightly (n = 50) and on-demand (n = 50) sildenafil groups were well-matched at baseline. Nightly sildenafil patients had worse EPIC urinary bother and urinary irritative/obstructive subscale scores at 3 and 6 months after RP, even after controlling for multiple variables. On mixed-model analyses, the differences between groups for these EPIC subscales (4.9 and 2.5, respectively) were greater than documented thresholds for clinical significance. Increasing nerve-sparing score was associated with improvements in EPIC urinary summary, bother, incontinence, and function scores; time from surgery was associated with improvements in all EPIC urinary health-related quality of life subscales. Conclusions: In this specific population and drug dose, we found that on-demand short-acting phosphodiesterase-5 inhibitor (PDE5i) dosing may be more effective after RP to maximize early urinary and erectile health-related quality of life. In preoperatively potent men, nightly sildenafil 50 mg impaired urinary health-related quality of life more than on-demand use in the early months after nerve-sparing RP, independent of effects on urinary continence.

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“…Relaxation of bladder neck was achieved with high levels of sildenafil in contracted human bladder neck by phenylephrine which suggests that PDE inhibitors may have potential effect to relax the bladder outlet. [19] The studies demonstrated the presence of PDE-5 in several parts of lower urinary tract vasculature. [13,20] Expression of PDE-5 was shown in the endothelial cell and vascular smooth muscles of the human prostatic urethra, prostate and bladder neck in immunohistochemical studies.…”

Section: Discussionmentioning

confidence: 97%

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model

Çalışkan

Keleş

Öztürk

et al. 2017

Turkish Journal of Urology

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Objective: Efficacy of treatments for benign prostate hyperplasia (BPH) is limited because the disease has complex etiopathogenesis. Recent studies have demonstrated the presence of phosphodiesterase-5 (PDE-5) receptors in prostate tissue. We investigated efficacy of sildenafil citrate in testosteron -induced BPH in rats. Material and methods:The rats were divided into three groups. Each groups had 7 rats. Group 1 was control group. Testosteron propionate 3 mg/kg/day was injected subcutaneously for two weeks in Group 2. The same procedure was done for Group 3 and sildenafil citrate was added to water at daily doses of 2 mg/kg for two weeks. The rats were euthanized with intraperitoneal pentobarbital. The body weights were measured and the prostates were removed. Results:The mean weights of rats were 288±31.93, 345±23.23 and 294±32.86 g in Groups 1, 2 and 3, respectively. The mean prostate weights of rats were 0.74±0.18, 1.3±0.13 and 0.72±0.24 g in Groups 1, 2, and 3, respectively. Group 2 had statistically significantly higher prostate weights than the other groups (p<0.01). Relative prostate weight is calculated with ratio of prostate weight to body weight. BPH group showed an increase in relative prostate weight compared with other groups with significant difference (p= 0.036 and p= 0.040). There was statistical difference for acinar area between Group 2 and the others, no significant difference of number of acini, interstitial space and epithelial thickness. Group 2 has more papillary projections per acini than the other groups. Conclusion:Favourable effect of sildenafil citrate on dimensions of prostate but not all on histological parameters was observed. We expect that PDE-5 inhibitors might be a treatment option for BPH patients if the studies support our findings in the future.

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Relaxant Effects of Sildenafil on the Human Isolated Bladder Neck

Cited by 28 publications

References 26 publications

Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events

Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events

Nightly sildenafil use after radical prostatectomy has adverse effects on urinary convalescence: Results from a randomized trial of nightly vs on-demand dosing regimens

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model

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