Oxidative stress reduces the muscarinic receptor function in the urinary bladder
Oxidative stress reduces the muscarinic receptor function in the urinary bladder
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DOI：
10.1002/nau.20298
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发表时间：
2007-01-01
影响因子：
2
通讯作者：
van Kerrebroeck, Philip E. V.
中科院分区：
文献类型：
--
作者：
de Jongh, Rik;Haenen, Guido R. M. M.;van Kerrebroeck, Philip E. V.
目的：膀胱中的几种病理生理状况，例如缺血/再灌注和炎症的特征在于活性氧（ROS）的形成。活性氧是剧毒的，因为它们可以破坏蛋白质，DNA和脂质。本研究的目的是探讨氧化应激对逼尿肌平滑肌兴奋-收缩偶联的影响。材料和方法：从猪膀胱中分离平滑肌条，并固定在器官浴槽中。通过向器官浴中添加氢过氧化枯烯（CHP）（一种亲脂性氢过氧化物）来模拟氧化应激。在加入CHP之前和之后监测对电场刺激（EFS：4-32 Hz）、卡巴胆碱（10（-8）-3 x 10（-5）M）、钾（65.3 mM）和ATP（1 mM）的收缩反应。结果：逼尿肌条对EFS的反应主要基于神经源性刺激和乙酰胆碱的释放。CLIP在相同程度上减少了对EFS和卡巴胆碱的收缩反应。卡巴胆碱浓度-响应曲线的pD值在暴露于0.1 mM、0.4 mM、0.8 mM CHP后显著降低。此外，卡巴胆碱获得的最大效应在0.1 mM、0.4 mM和0.8 mM CHP处理后显著降低。钾和ATP引起的收缩显着减少氧化应激的影响相比，EFS和卡巴胆碱引起的反应幅度相当。结论：我们的研究结果表明，由CHP诱导的氧化应激影响猪膀胱收缩力。毒蕈碱受体信号系统严重受损。L型钙通道和收缩系统受到的影响较小，胆碱能神经基本上不受影响。
Aims: Several pathophysiological conditions in the urinary bladder, for example, ischemia/reperfusion and inflammation are characterized by the formation of reactive oxygen species (ROS). The ROS are highly toxic because they can destroy proteins, DNA, and lipids. The aim of this study was to investigate the effect of oxidative stress on excitation-contraction coupling of detrusor smooth muscle. Materials and Methods: Smooth muscle strips were dissected from pig urinary bladder and mounted in organ baths. Oxidative stress was mimicked by the addition of Cumene hydroperoxide (CHP), a lipophilic hydroperoxide, to the organ baths. Contractile responses to electrical field stimulation (EFS: 4-32 Hz), carbachol (10(-8)-3 x 10(-5) M), potassium (65.3 mM), and ATP (1 mM) were monitored before and after the addition of CHP. Results: Responses of detrusor strips to EFS were for the greater part based on neurogenic stimulation and the release of acetylcho-line. CLIP diminished contractile responses to EFS and carbachol to the same extent. The pD-value of the carbachol concentration-response curve decreased significantly after exposure to 0.1 mM, 0.4 mM, 0.8 mM CHP Furthermore the maximal effect obtained with carbachol was significantly reduced after 0.1 mM, 0.4 mM, and 0.8 mM CHP treatment. Contractions induced by potassium and ATP were significantly less affected by oxidative stress compared to EFS- and carbachol-induced responses of comparable amplitude. Conclusions: The results of our study demonstrate that oxidative stress induced by CHP affects pig bladder contractility. The muscarinic receptor signaling system is severely damaged. L-type calcium channels and the contractile system are less affected and cholinergic nerves remain largely unaffected.