Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition

Adolfsson, Per; Ahlstrand, Christer; Varenhorst, Eberhard; Svensson, Samuel

doi:10.1002/pros.10077

Cited by 38 publications

(23 citation statements)

References 36 publications

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“…Examination of human tissues revealed similar findings (16,47). In addition to modulating SM tone by cGMP degradation, PDE5 also regulates cell proliferation (2,74). Zenzmaier et al (74) have reported that tadalafil reduces proliferation of primary prostate stromal cells and to a lesser extent primary prostate basal epithelial cells in a dose-dependent manner.…”

supporting

confidence: 52%

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Zhang

Zang

Wei

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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) plays a permissive role in the development of benign prostatic hyperplasia (BPH), and phosphodiesterase 5 inhibitors (PDE5is) have been found to be effective for BPH and lower urinary tract symptoms (LUTS) in clinical trials. This study investigated the effect of T on smooth muscle (SM) contractile and regulatory signaling pathways, including PDE5 expression and functional activity in prostate in male rats (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, real-time RT-PCR, Western blot analysis, and immunohistochemistry were performed. Castration heavily attenuated contractility, including sensitivity to phenylephrine with SM myosin immunostaining revealing a disrupted SM cell arrangement in the stroma. PDE5 was immunolocalized exclusively in the prostate stroma, and orchiectomy signficantly reduced PDE5 immunopositivity, mRNA, and protein expression, along with nNOS and ROK␤ mRNA, whereas it increased eNOS plus ␣ 1a and ␣1b adrenoreceptor expression in castrated animals. The PDE5i zaprinast significantly increased prostate strip relaxation to the nitric oxide donor sodium nitroprusside (SNP) in control but not castrated rats. But SNP alone was more effective on castrated rats, comparable with sham treated with SNP plus zaprinast. T supplementation prevented or restored all above changes, including SNP and zaprinast in vitro responsiveness. In conclusion, our data show that T positively regulates PDE5 expression and functional activities in prostate, and T ablation not only suppresses prostate size but also reduces prostatic SM contractility, with several potential SM contraction/relaxation pathways implicated. Zaprinast findings strongly suggest a major role for PDE5/cGMP in this signaling cascade. PDE5 inhibition may represent a novel mechanism for treatment of BPH. benign prostatic hyperplasia; contraction; lower urinary tract symptoms; phosphodiesterase 5; phosphodiesterase 5 inhibitors; smooth muscle myosin; nitric oxide BENIGN PROSTATIC HYPERPLASIA (BPH), a cause of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging men, is a common pathological process with a histological prevalence of ϳ50 -60% for men in their 60s and 80 -90% for men in their 70s and 80s (54). Although the etiology of prostatic hyperplasia is not well understood, androgens and aging are necessary for the development of BPH (55) containing two physiological components, static (increased prostate size) (40) and dynamic [increased prostatic smooth muscle (SM) tone] (11).The dynamic tone of prostatic SM is regulated mainly by the ␣ 1 -adrenoreceptor (72), with up to 50% of the total urethral pressure in BPH patients being attributed to ␣-adrenoreceptormediated muscle tone (18), and ␣ 1 -blockers are the first-line therapy for BPH. Three major subtypes of adrenoreceptors have been identified to exist in the prostate at the molecular level (␣ 1a , ␣ 1b , and ␣ 1d ) (15). Eckert et al. (14), using a patch clamp combined with the fura-2 fluorescence calcium labelin...

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supporting

confidence: 52%

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Zhang

Zang

Wei

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Recent reports suggests that cGMP accumulation could have an antiproliferative effect on smooth muscle cells of the prostate [20]. A previous report showed that Zaprinast can reduce proliferation in prostatic stromal cells and in cultured smooth muscle cells from patients with BPH [21,22]. Antiproliferative effect of all commercially available PDE5 inhibitors on BPH smooth muscle cells has been shown [9,22].…”

Section: Discussionmentioning

confidence: 95%

Uroflowmetric assessment of acute effects of sildenafil on the voiding of men with erectile dysfunction and symptomatic benign prostatic hyperplasia

et al. 2008

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“…Following accumulation of cGMP, hyperpolarization, rapid drop in intra--cytoplasmic calcium and finally relaxation of smooth muscle will happen (22,23). In vitro study showed that sildenafil inhibits the growth of prostatic smooth muscle cells (24). Inhibition of PDE-5 in the prostate may have a positive impact on dynamic component of LUTS by decreasing sympathetic tone (7).…”

Section: Discussionmentioning

confidence: 99%

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

et al. 2014

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ARTICLE INFO ______________________________________________________________ ______________________Objective: To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). Materials and Methods: 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient's ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results: Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). Conclusion: It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

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Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition

Cited by 38 publications

References 36 publications

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Uroflowmetric assessment of acute effects of sildenafil on the voiding of men with erectile dysfunction and symptomatic benign prostatic hyperplasia

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

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