Gillespie J I, Drake M J
The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, Newcastle upon Tyne NE2 4HH, UK.
BJU Int. 2004 Apr;93(6):851-8. doi: 10.1111/j.1464-410X.2003.04727.x.
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 degrees C. 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 micromol/L caused only small (<2 cmH(2)O) rises in intravesical pressure. In the presence of phasic activity induced by either muscarinic or nicotinic stimulation, SNP at > 30 micromol/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.
研究一氧化氮（NO）供体硝普钠（SNP）和磷酸二酯酶（PDE）抑制剂对豚鼠离体全膀胱激动剂刺激产生的阶段性活动的作用，这些药物据称会影响细胞内cGMP水平。
所有实验均使用来自雌性豚鼠（270 - 300 g）的离体全膀胱。每个膀胱通过尿道插管，并悬浮于33 - 35摄氏度含氧量充足的溶液的腔室中。记录膀胱压力，并将药理试剂添加到浸泡膀胱浆膜面的溶液中。
在未受刺激的膀胱中，高达300 μmol/L的SNP仅引起膀胱内压小幅（<2 cmH₂O）升高。在由毒蕈碱或烟碱刺激诱导的阶段性活动存在时，>30 μmol/L的SNP会使瞬态频率产生剂量依赖性增加。通过免疫荧光鉴定出对SNP有细胞内cGMP增加反应的细胞，它们位于膀胱上皮下层和肌束内。逼尿肌主体平滑肌细胞的cGMP未升高。暴露于cGMP/PDE抑制剂扎普司特对阶段性活动无影响，但暴露于双嘧达莫会使频率短暂升高，随后受到抑制。双嘧达莫还显著增加了阶段性活动的幅度。
这些数据表明NO/cGMP在膀胱阶段性活动的整合调节中起兴奋作用。可能涉及的一类细胞可能位于膀胱上皮下层和肌肉内。对影响cGMP的PDE抑制剂的不同敏感性表明，负责的细胞表达这些调节酶的特定同工型。讨论了这些观察结果的重要性、它们在膀胱整合生理学中的可能作用以及膀胱病理学的起源。
