Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.
Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.
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糖尿病减弱尿路上皮对逼尿肌收缩力和自发活动的调节。
DOI：
10.1111/iju.12491
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Davies,KelvinP
中科院分区：
文献类型：
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作者：
Wang,Yi;Tar,MosesT;Fu,Shibo;Melman,Arnold;Davies,KelvinP
ObjectivesTo探讨糖尿病对膀胱收缩功能的影响。方法制备8周龄链脲佐菌素诱导的糖尿病大鼠（n= 19）和非糖尿病对照大鼠（n= 10）的膀胱条（完整或裸露的膀胱）。MaxiK调节剂的作用（伊比利亚毒素和四乙铵）和Kv 7结果在非糖尿病动物的膀胱条中，尿激酶的存在导致MaxiK和Kv 7通道活性调节剂对卡巴胆碱诱导的力产生的显著敏感性，而在糖尿病动物中，尿路上皮对这些试剂的敏感性显著降低。来自非糖尿病动物的尿路上皮完整膀胱条在降低自发性阶段性收缩幅度方面对Kv 7活性调节剂更敏感，而在糖尿病动物中，存在或不存在尿路上皮并不改变对Kv 7活性调节剂的敏感性。自发活动中存在的四乙铵是不受urothorm在膀胱条从糖尿病或non-diabeticanimals.ConclusionsThe存在的urothorm在膀胱从非糖尿病动物调节钾受体阻滞剂的活性，影响膀胱收缩力，而在糖尿病膀胱这种效果减弱。这些发现可能有助于解释靶向钾通道的药物治疗缺乏成功，以治疗患有损害尿路上皮功能疾病的患者的膀胱病理。
ObjectivesTo investigate the effect of diabetes on urothelial modulation of bladder contractility.MethodsBladder strips (urothelium intact or denuded) were prepared from 8‐week‐old streptozotocin‐induced diabetic (n= 19) and non‐diabetic control rats (n= 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol‐induced force generation and spontaneous contractile activity.ResultsIn bladder strips from non‐diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol‐induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial‐intact bladder strips from non‐diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial‐denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non‐diabetic animals.ConclusionsThe presence of the urothelium in bladders from non‐diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function.