Aizawa Naoki, Sugiyama Rino, Ichihara Koji, Fujimura Tetsuya, Fukuhara Hiroshi, 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.
BJU Int. 2016 Jun;117(6):993-1001. doi: 10.1111/bju.13313. Epub 2015 Sep 28.
To clarify the involvement of bladder α1-adrenoceptors (α1-ARs) in afferent pathways by investigating the effects of silodosin and BMY7378, selective α1A- or α1D-AR antagonists, respectively, on single-unit afferent nerve fibre activity (SAA) of the primary bladder afferent nerves and their relationship with bladder microcontractions in rats.
A total of 63 female Sprague-Dawley rats were anaesthetized with urethane. The SAA of Aδ and C fibres generated from the left L6 dorsal roots was determined using electrical stimulation of the left pelvic nerve and bladder distension. After measuring baseline SAA during constant filling cystometry, the procedure was repeated with i.v. (0.3-30 μg/kg) or intravesical (10 μm) administration of each antagonist. In separate rats, the bladder was filled with saline until the intravesical pressure reached 30 cmH2 O, and was kept under isovolumetric conditions, then the recording was performed with i.v.-administered vehicle and silodosin (0.3 μg/kg).
A total of Aδ fibres and 33 C fibres were isolated from 63 rats. The SAA of Aδ fibres, but not C fibres, were dose-dependently decreased after both i.v. and intravesical administrations of each of the antagonists. In the experiments under bladder isovolumetric conditions, silodosin administration significantly decreased the SAA of Aδ fibres, but not C fibres, compared with vehicle administration. There were no significant effects on either the mean basal bladder pressure or microcontractions.
The present study suggests that both α1A- or α1D-ARs in the rat bladder are involved in the activation of the bladder mechanosensory Aδ fibres during bladder filling, and that this activation may not be related to bladder microcontractions.
通过分别研究选择性α1A - 肾上腺素能受体（α1A - AR）拮抗剂西洛多辛和α1D - AR拮抗剂BMY7378对大鼠初级膀胱传入神经的单单位传入神经纤维活动（SAA）的影响及其与膀胱微收缩的关系，来阐明膀胱α1 - 肾上腺素能受体（α1 - ARs）在传入通路中的作用。
总共63只雌性Sprague - Dawley大鼠用乌拉坦麻醉。通过电刺激左侧盆神经和膀胱扩张来测定源自左侧L6背根的Aδ和C纤维的SAA。在恒定充盈膀胱测压期间测量基线SAA后，静脉内（0.3 - 30μg / kg）或膀胱内（10μm）给予每种拮抗剂后重复该过程。在另外的大鼠中，膀胱用盐水充盈直至膀胱内压达到30 cmH2O，并保持在等容条件下，然后用静脉内给予的溶媒和西洛多辛（0.3μg / kg）进行记录。
从63只大鼠中总共分离出Aδ纤维和33根C纤维。静脉内和膀胱内给予每种拮抗剂后，Aδ纤维的SAA呈剂量依赖性降低，但C纤维的SAA未降低。在膀胱等容条件下的实验中，与给予溶媒相比，给予西洛多辛显著降低了Aδ纤维的SAA，但未降低C纤维的SAA。对平均基础膀胱压力或微收缩均无显著影响。
本研究表明，大鼠膀胱中的α1A - 或α1D - ARs均参与膀胱充盈期间膀胱机械感觉Aδ纤维的激活，并且这种激活可能与膀胱微收缩无关。
