Effects of Chronic Treatment With Cilostazol, a Phosphodiesterase 3 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model

Abstract

Tel; +81-166-68-2533, Fax; +81-166-68-2539, E-mail; matsums@asahikawa-med.ac.jp utnnin title Effect of PDE3i treatment on female rat obstructed bladder. Methods Twelve-week-old female Sprague-Dawley rats were divided into five groups; group 1 and 2, sham operated rats (each 4 rats); group 3-5, BOO rats (each 6 rats).Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high dose PDE3i diet, and group 4 rats were given low dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group.uestlts BOO induced a significant increase in bladder weight in group 3-5 compared with group 1 and 2. PDE3i treatment did not affect bladder weight in either sham or BOO rats.Contractile forces in response to EFS, carbachol and KCl in group 3 were about 20-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i treated BOO rats were not significantly different from those in normal diet treated BOO rats. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with normal diet treated BOO rats. ConcltsionsPDE3i has a small but significant protective effect on the contractile Matsumoto S, et al., Effect of PDE3i treatment on female rat obstructed bladder-3 -dysfunction induced by 4-weeks BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder. Matsumoto S, et al., Effect of PDE3i treatment on female rat obstructed bladder -4 - IntroductionLUTS are highly prevalent among elderly men and women, and have a significant impact on the patients' quality of life. The cause of LUTS is multifactorial and includes BOO, bladder ischemia, autonomic sympathetic overactivity, and so on [1]. Increasing evidence has shown that ischemia and reperfusion are major etiologic factors in the progression of bladder dysfunction induced by BOO, and that part of the damage is due to the generation of free radicals and the resultant cellular and subcellular membrane peroxidation [1]. The importance of ischemia as an etiologic factor in bladder dysfunction has been supported by recent animal studies in which bladder ischemia was experimentally created by BOO, bladder overdistension and atherosclerosis [2][3][4][5][6][7]. The evidence has suggested that bladder ischemia causes significant bladder dysfunction and leads to decreased contractile responses of the bladder.  1 -blocker has been shown to have a protective effect on bladder function of the rat after BOO or bladder overdistension possibly through an improvement of bladder ischemia [6,7]. In clinical practice, 1 -blocker is widely used as a first-line treatment for male patients with LUTS that are associated with BOO due to BPH (LUTS/BPH). 1 -...

Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2‐ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction

“…The SD rats were randomly divided into three groups: the sham-operated group ( n = 6), the BOO group ( n = 6), and the BOO+SFN group ( n = 6). The sham-operated group that underwent a sham operation was used as the control group, and BOO surgeries were applied to rats of the BOO group and the BOO+SFN group according to the method described previously [ 14 ]. Briefly, the rats were anesthetized with 10% chloral hydrate (3 mL/kg, intraperitoneally) and then fixed in a supine position.…”

Combination phosphodiesterase type 4 inhibitor and phosphodiesterase type 5 inhibitor treatment reduces non-voiding contraction in a rat model of overactive bladder

“…In our study, LUT weight after PBOO and either low or high dose combination treatment was not significantly different from sham PBOO, indicating that combination treatment could potentially lessen the effects of PBOO. Matsumoto et al tested cilostazol, a PDE3i, which did not significantly reduce bladder weight after four weeks of treatment [17]. It is unclear if the combination of PDE4i, which increases cAMP, and a PDE5i, which increases cGMP, would have a similar effect as a PDE3i, which increase cAMP and cGMP.…”

“…Twenty-six days after PBOO or sham PBOO a suprapubic bladder catheter was implanted followed by functional testing and euthanasia 2 days later. Female rats were used because the PBOO model of OAB is the most commonly done and most well validated in female rats [6,10,16,17].…”

Effect of Sulforaphane on Bladder Compliance in a Rat Model of Partial Bladder Outlet Obstruction

“…The bladder outlet was partially obstructed by the retropubic method described previously [11, 12]. Briefly, rats were anesthetized with 10% chloral hydrate and then placed in a supine position.…”