Sugiyama Rino, Aizawa Naoki, Ito Hiroki, Fujimura Tetsuya, Suzuki Motofumi, Nakagawa Tohru, Fukuhara Hiroshi, Kume Haruki, Homma Yukio, Igawa Yasuhiko
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Low Urin Tract Symptoms. 2017 May;9(2):94-101. doi: 10.1111/luts.12109. Epub 2015 Jul 27.
To investigate single or combined effect of silodosin, an α1A-adrenoceptor antagonist, and imidafenacin, an antimuscarinic agent, on bladder function in a subacute bladder outlet obstruction (BOO) model of male rats.
Partial BOO was created in male Wistar rats by ligating the urethra with a steel rod. On day 10 after surgery, when frequent voiding was most remarkable on voiding behavior measurement in a metabolic cage, cystometric investigations in a conscious restrained condition were conducted with cumulative intravenous administration of silodosin alone (0.1, 1, 10, and 100 µg/kg), imidafenacin alone (1, 3, and 10 µg/kg), or a combination of the two drugs.
When compared with the Sham rats, the BOO rats showed an increase in bladder capacity, residual volume, mean amplitude and the number of non-voiding contractions (NVCs), accompanied with an increase in bladder weight. In the BOO rats, silodosin alone at 100 µg/kg significantly decreased the number of NVCs, whereas imidafenacin alone at 3 and 10 µg/kg significantly decreased both the number and mean amplitude of NVCs. The combination administration with lower doses (silodosin at 10 µg/kg and imidafenacin at 1 µg/kg) significantly suppressed both the number and mean amplitude of NVCs.
The present results indicate a suppressive effect of silodosin or imidafenacin alone and a synergic effect of the combination of these two drugs on NVCs in a subacute BOO model of male rats.
在雄性大鼠亚急性膀胱出口梗阻（BOO）模型中，研究α1A肾上腺素能受体拮抗剂西洛多辛和抗毒蕈碱药物咪达非那新对膀胱功能的单一或联合作用。
通过用钢棒结扎尿道在雄性Wistar大鼠中制造部分BOO。在手术后第10天，当在代谢笼中进行排尿行为测量时频繁排尿最为明显时，在清醒约束条件下进行膀胱测压研究，单独累积静脉注射西洛多辛（0.1、1、10和100μg/kg）、单独咪达非那新（1、3和10μg/kg）或两种药物联合使用。
与假手术大鼠相比，BOO大鼠的膀胱容量、残余尿量、平均幅度和非排尿收缩（NVCs）次数增加，同时膀胱重量增加。在BOO大鼠中，单独使用100μg/kg西洛多辛可显著减少NVCs次数，而单独使用3和10μg/kg咪达非那新可显著减少NVCs次数和平均幅度。较低剂量联合给药（10μg/kg西洛多辛和1μg/kg咪达非那新）可显著抑制NVCs次数和平均幅度。
目前的结果表明，在雄性大鼠亚急性BOO模型中，西洛多辛或咪达非那新单独使用具有抑制作用，这两种药物联合使用对NVCs具有协同作用。
