The effect of sildenafil citrate on bladder outlet obstruction: a mouse model.
ABSTRACT To investigate if sildenafil citrate can inhibit the functional and structural changes of the detrusor in a murine model of bladder outlet obstruction (BOO). Phosphodiesterase type 5 (PDE-5) inhibitors have recently been used for treating urinary symptoms associated with prostatic obstruction, but it is unclear whether PDE-5 inhibition acts on the prostatic urethra or the bladder.
In 18 male Balb/CAN mice, partial BOO was created and the mice allowed to survive for 6 weeks. Half of the mice (nine) were treated with oral sildenafil citrate daily (10 mg/kg) by oral lavage (BOO + V), and half (nine) were not (BOO). Six mice were used as sham-operated controls and received no sildenafil. The mice were assessed by urodynamics at baseline and after 6 weeks, with a measurement of volume at first uninhibited non-voiding contraction (V(DO1)), bladder capacity (BC), and detrusor pressure during void (Pdet). At 6 weeks, bladders were harvested, fixed and sectioned, and stained with haematoxylin and eosin (H&E) and trichrome stain. Detrusor muscle hypertrophy and fibrosis were evaluated on a scale of 1 (decreased) to 3 (increased), by two urologists and one pathologist unaware of the treatment group; the results were compared with those from normal controls.
BOO mice had a significantly greater BC than control mice, with a mean (SD) of 153 (66) vs 58 (13) microL (P = 0.004). Treatment with sildenafil did not significantly alter BC. BOO caused an increase in Pdet compared to controls, with a mean (SD) of 25 (7) vs 12 (5) cm H2O. P(det) was not significantly different after treatment with sildenafil. The median V(DO1) as a percentage of BC was significantly lower in BOO than in control mice (20% vs 53%, P > 0.03) and increased significantly after sildenafil treatment (20% vs 44%, P = 0.04). BOO was associated with a greater bladder weight than in control mice, with a mean (SD) of 89 (32) vs 27 (6) mg (P = 0.001), which was decreased with sildenafil treatment, to 40 (14) vs 89 (32) mg (P = 0.013). BOO caused an increase in detrusor muscular hypertrophy vs control mice, with a median H&E score of 3 vs 2 (P = 0.01) and an increase in fibrosis vs control mice, with a median trichrome score of 3 vs 2 (P = 0.01). BOO + V mice had reduced muscular hypertrophy and fibrosis, with a median H&E score of 3 vs 2 (P = 0.01) and a median trichrome score of 3 vs 1 (P = 0.01).
BOO mediates both functional and structural changes in the mouse bladder. Six weeks of obstruction caused an increase in BC, detrusor overactivity and voiding pressure, and mediated an increase in bladder weight, detrusor muscle hypertrophy and collagen deposition in the lamina propria and smooth muscle. Treatment with 6 weeks of oral sildenafil beginning at the time of BOO prevented the increase in detrusor overactivity without affecting voiding pressures, and prevented the increase in detrusor muscle hypertrophy and collagen deposition that otherwise occurred with BOO. It appears therefore that sildenafil citrate acts on the bladder rather than on the outlet.
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ABSTRACT: Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction.BMC Urology 05/2014; 14(1):44. DOI:10.1186/1471-2490-14-44 · 1.94 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: Bladder deterioration after partial outlet obstruction (pBOO) occurs commonly and has significant clinical implications. Our previous animal model results described the progression of pBOO to hypertrophy and fibrosis. We wished to determine if the pathologic process of pBOO can be altered with rationally chosen oral medications. Female Sprague-Dawley rats underwent controlled surgically induced pBOO. Rats were maintained for a period of 16 weeks at which point urodynamics were performed, and organs harvested. Rats were divided into four groups, each receiving different daily treatment: control (saline), oxybutynin (3 mg/kg), rapamycin (2 mg/kg), and tadalafil (2 mg/kg). Outcomes were assessed after 4,8,12, or 16 weeks. Measures included animal health, urodynamics, histology, mass spectrometry for collagen content, and rtPCR for inflammatory mediators. Rapamycin treated animals exhibited significant mortality at later time points. Oxybutinin and tadalafil treated bladders demonstrated significant improvements in bladder capacity and compliance, with less detrusor hypertrophy than controls. Tadalafil also resulted in a significant down-regulation of HIF-1α, while decorin, biglycan, and TGF-β were upregulated in treated animals. Tadalafil treated bladders measured lower collagen content towards the end of the study, indicating an antifibrotic effect. Our study has effectively demonstrated that deleterious changes secondary to pBOO can be altered pharmacologically. Oxybutinin and tadalafil seem to have a time-dependent protective effect on the detrusor muscle, although with different mechanisms of action. Tadalafil treatment in this setting appears to have an antifibrotic effect. This work has the potential to seed important clinical studies and improve clinical practice. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.Neurourology and Urodynamics 11/2013; DOI:10.1002/nau.22528 · 2.67 Impact Factor
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ABSTRACT: A simple sequential extraction technique is presented for the examination of PAH speciation in aquatic sediments. This method is discussed with special emphasis on the sorption of PAH to humic substances and coal-like particles. Sorption experiments were carried out with sediments after treatment with H2O2 or after lipid removal by organic solvent extraction. The results show that lipids exert only a minor influence on PAH sorption. Furthermore, deviations from simple partition behaviour are discussed.Bindungsformen polycyclischer aromatischer Kohlenwasserstoffe (PAK) in GewässersedimentenEine einfache sequentielle Extraktion zur Untersuchung der Bindungsform polycyclischer aromatischer Kohlenwasserstoffe (PAK) in Gewässersedimenten wird vorgestellt. Die Methode wird im Hinblick auf die Sorption von PAK an Huminstoffen und kohleähnliche Partikel diskutiert. Weiterhin wurden Sorptionsexperimente mit Sedimenten durchgeführt, die durch Behandlung mit H2O2 oder durch Extraktion der Lipide mit organischem Lösungsmittel erhalten wurden. Die Ergebnisse zeigen, daß die Lipide bezüglich der PAK-Sorption nur eine untergeordnete Rolle spielen und daß das Sorptionsverhalten nicht durch einen einfachen Verteilungsvorgang beschrieben werden kann.Fuel and Energy Abstracts 05/1996; 37(3):229-229. DOI:10.1016/0140-6701(96)89237-X