Fovaeus M, Andersson K E, Hedlund H
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
J Urol. 1989 Mar;141(3):637-40. doi: 10.1016/s0022-5347(17)40922-0.
The need for effective symptomatic treatment of patients with detrusor hyperactivity is widely recognized. In search of new principles of decreasing bladder contraction we have studied the effects of pinacidil on the isolated human bladder. Pinacidil is a recently developed antihypertensive agent classified as a K+ channel opener, and is believed to depress smooth muscle activity by this action. Pinacidil concentration-dependently depressed contractions elicited by carbachol, low concentrations of K+ (less than 60 mM) and electrical stimulation. In addition it caused a concentration-related increase in the efflux of 86Rb from preloaded detrusor cells. The effects on 86Rb efflux could be inhibited by tetraethylammonium chloride and procaine, but not by apamin, agents known to block K+-channels. The results support the view that part of the pinacidil effect on the human bladder is caused by an opening of K+-channels, efflux of K+ and subsequent hyperpolarization of the detrusor cells. Clinical testing of this new therapeutic principle for treatment of bladder hyperactivity seems justified.
逼尿肌功能亢进患者需要有效的对症治疗，这一点已得到广泛认可。为了探寻降低膀胱收缩的新原理，我们研究了吡那地尔对离体人膀胱的作用。吡那地尔是一种最近研制出的降压药，归类为钾通道开放剂，据信通过这种作用抑制平滑肌活动。吡那地尔浓度依赖性地抑制由卡巴胆碱、低浓度钾离子（低于60 mM）和电刺激引起的收缩。此外，它使预加载的逼尿肌细胞中86Rb的外流呈浓度相关增加。对86Rb外流的作用可被四乙铵和普鲁卡因抑制，但不能被已知能阻断钾通道的蜂毒明肽抑制。这些结果支持这样一种观点，即吡那地尔对人膀胱的部分作用是由钾通道开放、钾离子外流以及随后逼尿肌细胞超极化引起的。对这种治疗膀胱功能亢进的新治疗原理进行临床试验似乎是合理的。
