The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder
The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder
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DOI：
10.1111/j.1464-410x.2003.04727.x
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发表时间：
2004-04-01
影响因子：
4.5
通讯作者：
Drake, MJ
中科院分区：
文献类型：
--
作者：
Gillespie, JI;Drake, MJ
为了研究一氧化氮 (NO) 供体硝普钠 (SNP) 和磷酸二酯酶 (PDE) 抑制剂（旨在影响细胞内 cGMP 水平）对激动剂刺激豚鼠离体整个膀胱产生的阶段性活性的作用。所有实验均使用雌性豚鼠 (270-300 g) 的离体整个膀胱。 实验。每个膀胱通过尿道插管并悬浮在含有33-35℃含氧溶液的室中。记录膀胱压力，并将药物添加到沐浴膀胱近腔表面的溶液中。在未刺激的膀胱中，高达 300 μmol/L 的 SNP 只引起很小的（30 μmol/L），产生剂量依赖性的瞬变频率增加。通过免疫荧光鉴定对 SNP 做出反应并增加细胞内 cGMP 的细胞，并且处于 尿路上皮下层和肌束内。逼尿肌体的平滑肌细胞的 cGMP 没有表现出升高。暴露于 cGMP/PDE 抑制剂扎普司特对阶段性活动没有影响，但暴露于双嘧达莫会导致频率短暂上升，随后出现抑制。双嘧达莫还显着增加了阶段性活动的幅度。这些数据表明 NO/cGMP 在阶段性膀胱活动综合调节中的兴奋作用。可能涉及的一组细胞可能位于尿路上皮下层和肌肉内。对影响 cGMP 的 PDE 抑制剂的不同敏感性表明，负责表达这些调节酶的特定亚型的细胞。这些观察结果的重要性、它们在膀胱综合生理学中可能发挥的作用以及 讨论了膀胱病理学的起源。
To investigate the actions of the nitric oxide (NO) donor sodium nitroprusside (SNP) and phosphodiesterase (PDE) inhibitors, which purport to affect intracellular cGMP levels, on the phasic activity generated by agonist stimulation of the isolated whole bladder of the guinea pig.Isolated whole bladders from female guinea pigs (270-300 g) were used in all experiments. Each bladder was cannulated via the urethra and suspended in a chamber containing oxygenated solution at 33-35 degreesC. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder.In the unstimulated bladder, SNP at up to 300 mumol/L caused only small ( 30 mumol/L, produced a dose-dependent increase in the frequency of the transients. The cells responding to SNP with an increase in intracellular cGMP were identified by immunofluorescence, and were in the suburothelial layer and within the muscle bundles. Smooth muscle cells of the detrusor body did not show a rise in cGMP. Exposure to the cGMP/PDE inhibitor zaprinast had no effect on phasic activity, but exposure to dipyridamole produced a transient rise in frequency, followed by an inhibition. Dipyridamole also significantly increased the amplitude of the phasic activity.These data show an excitatory role for NO/cGMP in the integrated regulation of phasic bladder activity. One population of cells which may be involved may be in the suburothelial layer and within the muscles. The differential sensitivity to PDE inhibitors affecting cGMP suggests that the cells responsible express specific isoforms of these regulatory enzymes. The importance of these observations, their possible role in the integrated physiology of the bladder and origins of bladder pathology, are discussed.