The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction

Gumrah, A.; Tanıdır, Yılören; Tınay, İlker; Özyürek, Mustafa; Tarcan, Tufan

doi:10.1002/nau.23155

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…As shown in previous studies, the role of cytokines including alpha-blockers, antimuscarinics, and β-Adrenergic receptors during BOO has been well-established (Dale et al, 2014;Gumrah et al, 2017;Yamada et al, 2018). In addition, TGF-β signaling could stimulate fibrotic changes in BSMCs after BOO, and miR-133 could modulate TGF-β-induced BSMC phenotypic changes by targeting CTGF (Duan et al, 2015).…”

Section: Introductionmentioning

confidence: 75%

RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy

Chen

Chen²,

Di³

et al. 2022

Front. Cell Dev. Biol.

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Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo.Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression.Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA.Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

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Section: Introductionmentioning

confidence: 75%

RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy

Chen

Chen²,

Di³

et al. 2022

Front. Cell Dev. Biol.

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“…Sildenafil is a phosphodiesterase 5 (PDE-5) inhibitor; it inhibits the breakdown of cGMP thus prolongs the action of NO in smooth muscles [30]. Gumrah et al (2017) proved that sildenafil reduced bladder contractility in rats and Aizawa et al (2017) showed that sildenafil may improve bladder storage in female rats by exhibiting an inhibitory role on the bladder afferent transduction [31,32].…”

Section: Introductionmentioning

confidence: 99%

Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro

Bassiouni

Senbel

Norel

et al. 2019

Pharmacological Reports

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Background: Sildenafil (PDE5-inhibitor) and alprostadil (PGE 1 ) are used in combination clinically for the management of some cases of erectile dysfunction. Despite the roles of prostaglandins (PG) and NO pathways in contractility of bladder smooth muscle are frequently studied, the effect of sildenafil/alprostadil combination and the crosstalk between NO/cGMP and PG pathways on bladder activity is not documented.Methods: Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS,4Hz,80V,1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean±SEM (n=5-7).Results: Alprostadil(0.01-10µM) concentration-dependently potentiated ACh(100µM)-and EFS(4Hz)-induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40±5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1µM), but inhibited it at higher ones (10-100µM). IBMX (non-selective PDE-inhibitor, 10nM-100µM) and SNP (NO-donor, 1nM-1mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1µM), L-NAME (non-selective NOS-inhibitor, 100µM), N-PLA (nNOS-inhibitor, 30µM) or MB (nonselective GC-inhibitor, 10µM). In presence of sildenafil (0.1µM), the concentration-response curve of alprostadil (0.01-10µM) on both ACh and EFS-induced contraction was clearly shifted downward. Conclusions:A crosstalk between PGE 1 and NO/cGMP pathways may exist. At low concentrations only, the effect of sildenafil on bladder contractility is dependent on NO/cGMP. cGMP intracellularly-elevated by sildenafil, may inhibit the activity of PLC and hence the cascade of EP 1 -receptors, thus masking the hyperactivity of bladder caused by alprostadil, which adds to the advantages of this combination.

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Expression of NGF, MCP-1, uroplakin III, and NOS in bladder urothelium after partial urethral obstruction in rats

Öztürk

Çetinkaya

Düzcü

et al. 2020

Journal of Pediatric Urology

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The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction

Cited by 4 publications

References 34 publications

RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy

RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy

Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro

Expression of NGF, MCP-1, uroplakin III, and NOS in bladder urothelium after partial urethral obstruction in rats

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