Lee J G, Levin R M, Krasnopolsky L, Wein A J, Longhurst P A
Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, USA.
J Urol. 1995 Sep;154(3):1217-21.
The present studies were designed to determine the effects of in vivo and in vitro administration of ICI 198,615 (ICI), a leukotriene receptor antagonist, on the inflammatory changes that occur in the bladder after sensitization with ovalbumin.
The effect of intravenous administration of ICI on urodynamic changes after instillation of ovalbumin to sensitized guinea pigs was evaluated by in vivo cystometry. Responses of in vitro bladder muscle strips to contractile stimuli and ovalbumin were also evaluated in the presence of ICI.
In sensitized guinea pigs, in vivo cystometry with ovalbumin induced a marked decrease in bladder capacity and increase in intravesical pressure. Pretreatment with ICI prior to cystometry prevented the ovalbumin-induced changes in capacity and intravesical pressure. There were no significant differences between control and sensitized animals in the responses of in vitro bladder muscle strips to field stimulation or bethanechol. However, maximal contractile responses to ovalbumin were significantly greater in the strips from sensitized animals than in controls. Preincubation with ICI, indomethacin, or pyrilamine alone was unable to inhibit the contractile responses to ovalbumin. However, combined administration of ICI, indomethacin and pyrilamine completely blocked the responses.
In vivo administration of the leukotriene receptor antagonist ICI 198,615 reversed the urodynamic changes induced by ovalbumin challenge in sensitized guinea pigs. These results indicate that leukotrienes are primarily responsible for the changes in in vivo bladder function associated with sensitization.
本研究旨在确定白三烯受体拮抗剂ICI 198,615（ICI）体内和体外给药对卵清蛋白致敏后膀胱发生的炎症变化的影响。
通过体内膀胱测压评估静脉注射ICI对致敏豚鼠灌注卵清蛋白后尿动力学变化的影响。在有ICI存在的情况下，还评估了体外膀胱肌条对收缩刺激和卵清蛋白的反应。
在致敏豚鼠中，卵清蛋白的体内膀胱测压导致膀胱容量显著降低和膀胱内压升高。膀胱测压前用ICI预处理可防止卵清蛋白诱导的容量和膀胱内压变化。体外膀胱肌条对场刺激或氨甲酰甲胆碱的反应在对照动物和致敏动物之间没有显著差异。然而，致敏动物肌条对卵清蛋白的最大收缩反应明显大于对照动物。单独用ICI、吲哚美辛或吡苄明预孵育不能抑制对卵清蛋白的收缩反应。然而，ICI、吲哚美辛和吡苄明联合给药完全阻断了反应。
白三烯受体拮抗剂ICI 198,615的体内给药逆转了致敏豚鼠卵清蛋白激发诱导的尿动力学变化。这些结果表明白三烯是致敏相关的体内膀胱功能变化的主要原因。
