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: 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
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ABSTRACT: Alpha-blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.Current Urology Reports 08/2008; 9(4):295-301. DOI:10.1007/s11918-008-0005-3 · 1.51 Impact Factor