Akino Hironobu, Ito Hideaki, Nagase Keiko, Matsuta Yosuke, Aoki Yoshitaka, Hattori Tsuyoshi, Yokoyama Osamu
Department of Urology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan.
Int J Urol. 2019 Sep;26(9):924-930. doi: 10.1111/iju.14069. Epub 2019 Jul 17.
To elucidate the mechanism of action of the α -blocker, naftopidil, in partial bladder outlet obstruction animals, by studying non-voiding contractions, and the levels of mediators were measured with resiniferatoxin treatment.
A total of 35 female Wistar rats were randomly divided into a sham or bladder outlet obstruction group, and rats in each group were given vehicle or resiniferatoxin. Incomplete urethral ligation was applied to the bladder outlet obstruction group. After cystometry, the intravesical level of prostaglandin E and adenosine 5'-triphosphate was measured in the instilled perfusate collected. Naftopidil was given at the time of cystometry.
In bladder outlet obstruction rats, non-voiding contractions, bladder capacity, and the intravesical levels of prostaglandin E and adenosine 5'-triphosphate were markedly increased compared with sham rats. Naftopidil decreased non-voiding contractions, enlarged the bladder capacity, and decreased the intravesical levels of prostaglandin E and adenosine 5'-triphosphate. Resiniferatoxin enhanced non-voiding contractions. The effects of naftopidil on non-voiding contractions and the intravesical level of prostaglandin E , but not adenosine 5'-triphosphate, were tolerant to resiniferatoxin.
In bladder outlet obstruction rats, one cause of generation of non-voiding contractions might be bladder wall distension, but not transient receptor potential cation channel V1. The increase in intravesical prostaglandin E might also be associated with the generation of non-voiding contractions. Naftopidil inhibits the increase in non-voiding contractions and decreases the intravesical level of prostaglandin E , which are independent of transient receptor potential cation channel V1.
通过研究无排尿收缩，并测量树脂毒素处理后介质水平，阐明α受体阻滞剂萘哌地尔在部分膀胱出口梗阻动物中的作用机制。
将35只雌性Wistar大鼠随机分为假手术组或膀胱出口梗阻组，每组大鼠给予溶剂或树脂毒素。对膀胱出口梗阻组施行不完全尿道结扎。膀胱测压后，测量收集的灌注液中膀胱内前列腺素E和5'-三磷酸腺苷的水平。在膀胱测压时给予萘哌地尔。
与假手术大鼠相比，膀胱出口梗阻大鼠的无排尿收缩、膀胱容量以及膀胱内前列腺素E和5'-三磷酸腺苷水平显著增加。萘哌地尔减少无排尿收缩，扩大膀胱容量，并降低膀胱内前列腺素E和5'-三磷酸腺苷水平。树脂毒素增强无排尿收缩。萘哌地尔对无排尿收缩和膀胱内前列腺素E水平（而非5'-三磷酸腺苷水平）的作用对树脂毒素具有耐受性。
在膀胱出口梗阻大鼠中，无排尿收缩产生的一个原因可能是膀胱壁扩张，而非瞬时受体电位阳离子通道V1。膀胱内前列腺素E的增加也可能与无排尿收缩的产生有关。萘哌地尔抑制无排尿收缩的增加并降低膀胱内前列腺素E水平，这与瞬时受体电位阳离子通道V1无关。
