Applied Pharmacology Research Laboratories, Astellas Pharma, Inc., Tsukuba, Japan.
J Urol. 2011 Dec;186(6):2470-7. doi: 10.1016/j.juro.2011.07.085. Epub 2011 Oct 21.
Decreased bladder blood flow was the subject of a recent study as a pathophysiological cause of bladder overactivity. We developed a rat model of bladder over distention/emptying induced bladder overactivity and investigated the effect of the α(1)-adrenoceptor antagonist tamsulosin on bladder blood flow and bladder function in this model.
The bladder was distended with 2 ml saline using anesthesia for 2 hours (over distention) and then emptied. Bladder blood flow was measured using a perfusion imager. Micturition behavior and parameters were observed using a metabolic cage and a cystometry method, respectively, from 2 hours after bladder emptying. After model establishment was confirmed we examined the participation of afferent C-fibers and the effects of tamsulosin in rats pretreated with capsaicin (Sigma-Aldrich®) (125 mg/kg) and tamsulosin (1 μg/kg per hour), respectively, using a metabolic cage.
Decreased bladder blood flow was observed upon over distention with partial recovery at emptying. Bladder over distention/emptying increased micturition frequency and decreased mean voided volume in the micturition recording study, and decreased the intercontraction interval and voided volume without affecting micturition pressure, threshold pressure or post-void residual volume in the cystometry study. Capsaicin pretreatment did not affect bladder overactivity. However, 1-week continuous treatment with tamsulosin increased bladder blood flow after bladder emptying, resulting in decreased micturition frequency and increased voided volume.
Bladder over distention/emptying induced bladder blood flow decrease/partial recovery and caused bladder overactivity via a mechanism other than capsaicin sensitive C-fiber activation. Findings in tamsulosin treated rats confirmed the potency of tamsulosin to increase bladder blood flow and ameliorate bladder overactivity.
近期的一项研究关注于膀胱血流减少，认为其是膀胱过度活动的病理生理学原因。我们建立了一种膀胱过度扩张/排空诱导的膀胱过度活动大鼠模型，并在此模型中研究了α(1)-肾上腺素能受体拮抗剂坦索罗辛对膀胱血流和膀胱功能的影响。
通过麻醉将 2ml 生理盐水注入膀胱 2 小时（过度扩张），然后排空。使用灌注成像仪测量膀胱血流。通过代谢笼观察排尿行为和参数，通过尿动力学方法测量膀胱排空后 2 小时的排尿参数。在确认模型建立后，我们分别使用代谢笼和膀胱测压法在预先用辣椒素（Sigma-Aldrich®）（125mg/kg）和坦索罗辛（1μg/kg/小时）预处理的大鼠中观察传入 C 纤维的参与和坦索罗辛的作用。
膀胱过度扩张导致膀胱血流减少，排空时部分恢复。膀胱过度扩张/排空增加了排尿频率，减少了排尿记录研究中的平均排尿量，减少了两次收缩之间的间隔和排空量，而不影响排尿压、阈值压或膀胱测压研究中的排空后残余尿量。辣椒素预处理不影响膀胱过度活动。然而，坦索罗辛连续治疗 1 周后增加了膀胱排空后的膀胱血流，导致排尿频率降低，排尿量增加。
膀胱过度扩张/排空导致膀胱血流减少/部分恢复，并通过与辣椒素敏感 C 纤维激活无关的机制引起膀胱过度活动。坦索罗辛治疗大鼠的结果证实了坦索罗辛增加膀胱血流和改善膀胱过度活动的效力。
