27 The same investigators reported the effects of captopril (1 mg/kg per day), which was subcutaneously administered by an osmotic pump for 2 weeks, on bladder weight, total DNA, protein and collagen content in 2-day-old (neonatal) rabbits that were subjected to BOO. Captopril treatment significantly inhibited the BOO-induced increase in total DNA and reduced the total amount of collagen. Consistent with these results,

histological Ganetespib price analysis indicated that captopril inhibited the serosal hyperplasia and collagen deposition that is associated with bladder obstruction.28 Such disparity between the results of these studies may be due to species or age-specific effects. In contrast, our recent data show that losartan treatment prevents bladder hypertrophy, fibrosis, Palbociclib chemical structure and dysfunction related to bladder obstruction in 12-week-old male rats. In our experiments, Sprague-Dawley rats underwent surgery to produce partial bladder outlet obstruction (BOO rats; n = 32) or sham surgery (sham group; n = 16). Two weeks later, 16 BOO rats were administered losartan subcutaneously at a rate of 3 mg/kg per day (losartan group) for 4 weeks using an osmotic pump; the remaining BOO rats received vehicle. The dose chosen was based on published data. It is believed that this dose does not affect

blood pressure in rat.30 Six weeks after surgery, continuous cystometry was performed in eight rats of each group, and the bladder was removed from the remaining rats. Bladder weight was measured, and each bladder was used for analysis of muscle strip contraction, Elastica-Masson staining,

and HB-EGF mRNA expression. Bladder weight markedly increased following BOO (827 ± 199 mg) and losartan treatment (519 ± 37 mg) suppressed this increase. Micturition pressure, which was significantly higher following BOO, was unaffected by losartan. The shortened micturition interval and decreased micturition volume in BOO rats were significantly prolonged and increased by losartan treatment. Losartan treatment also significantly decreased residual urine and further prolonged bladder contraction time (Fig. 1, Table 1). On histological examination, the collagen fiber-to-smooth muscle mafosfamide ratio in the bladder’s muscular layer was significantly increased in the BOO group (0.82 ± 0.19) compared to the sham group (0.56 ± 0.12); this increase was suppressed by losartan treatment (0.45 ± 0.11) (Fig. 2). HB-EGF mRNA expression, significantly increased following BOO and was significantly reduced by losartan treatment (Fig. 3). Losartan treatment increased the maximal contraction for all stimuli except for AngII compared to the BOO group. The bladder contractile response to AngII was similar for the sham and the BOO groups, while it disappeared with losartan treatment (Fig. 4). Our findings are in conflict with the above-mentioned reports of BOO rats.