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首页> 外文期刊>BJU international >In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats.
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In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats.

机译：在体内评估大鼠中ATP敏感性钾通道开放剂（-）-cromakalim，ZD6169和WAY-133537的效力和膀胱血管选择性。

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OBJECTIVE: To compare in vivo the potency and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs) (-)-cromakalim, WAY-133537 and ZD6169 and a muscarinic antagonist, tolterodine in rats. MATERIALS AND METHODS: Bladder and arterial pressures were monitored simultaneously, before and after increasing intravenous doses of compounds, in each of two urethane-anaesthetized rat bladder hyperactivity models: spontaneous non-voiding myogenic contractions secondary to partial outlet obstruction and volume-induced neurogenic contractions. RESULTS: (-)-Cromakalim, WAY-133537 and ZD6169 caused a dose-dependent suppression of spontaneous contractions in the obstructed model, with a 50% inhibition of the contraction area under the curve at doses of 0.06, 0.14 and 2.4 micro mol/kg (intravenous), respectively. Corresponding decreases in mean arterial pressure at these effective doses were 24%, 15% and 15%, respectively. The KCO potency rank order was the same and their relative potency highly comparable in the neurogenic model. There was complete inhibition of spontaneous contractions in obstructed rats at doses corresponding to approximately 50% inhibition of the neurogenic contractions. While tolterodine caused a dose-dependent inhibition of contractions in the neurogenic model, it was ineffective at inhibiting non-voiding contractions in obstructed rats. CONCLUSIONS: All KCOs tested caused significant decreases in arterial pressure at doses effective on the bladder in the model of obstructive instability, suggesting a lack of bladder-vascular selectivity. Similar KCO potency in both assays suggests no appreciable changes in KATP channel function as a result of partial outlet obstruction.
机译：目的：比较体内ATP敏感性钾通道开放剂（KCOs）（-）-cromakalim，WAY-133537和ZD6169以及毒蕈碱拮抗剂托特罗定的功效和膀胱血管选择性。材料和方法：在两种氨基甲酸乙酯麻醉的大鼠膀胱过度活动症模型中，分别在增加静脉注射化合物的剂量之前和之后同时监测膀胱和动脉压：自发性非空洞性肌源性收缩，继发于部分出口梗阻和体积诱导的神经源性收缩。结果：（-）-克罗麦卡林，WAY-133537和ZD6169在阻塞模型中引起剂量依赖性的自发收缩抑制，剂量为0.06、0.14和2.4 micro mol /时曲线下的收缩面积抑制50％。千克（静脉）。在这些有效剂量下，平均动脉压相应降低分别为24％，15％和15％。在神经生成模型中，KCO效能等级顺序相同，并且它们的相对效能高度可比。在阻塞的大鼠中，自发性收缩被完全抑制，其剂量相当于抑制神经源性收缩的50％。尽管托特罗定在神经源性模型中引起了剂量依赖性的收缩抑制，但它在抑制阻塞大鼠的无排泄性收缩方面无效。结论：在阻塞性不稳定模型中，所有测试的KCO均以对膀胱有效的剂量引起动脉压显着下降，表明缺乏膀胱血管选择性。两种测定中相似的KCO效能表明，由于部分出口阻塞，KATP通道功能没有明显变化。

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