Study in the role of nitric oxide (NO) and advanced glycation end products (AGE) on bladder function

一氧化氮（NO）是在生理和病理生理条件下调控下尿路功能的重要分子之一。此外，已经证明晚期糖基化终产物（AGE）通过各种组织中的AGE受体对细胞功能的损害起作用。在这项研究中，我们评估了NO和AGE对膀胱功能的作用。在大鼠和人逼尿肌标本中，NADPH-diaphorase染色和nNOS免疫组化染色显示nadph阳性和nNOS阳性神经元，与尿道和前列腺标本相比明显减少。在功能实验中，电场刺激（EFS）对人膀胱和兔膀胱分离的平滑肌条未引起明显的松弛反应。然而，L-NNA（一种NOS抑制剂）引起efs诱导的家兔胆碱能神经末梢乙酰胆碱（ACh）释放显著增加。提示NO对膀胱内乙酰胆碱释放有抑制作用，可能导致排尿周期充盈期膀胱容量增加，逼尿肌不稳定性降低。人逼尿肌标本有AGE形成。老年患者的age形成率明显高于老年患者，年龄与age形成率呈显著正相关。相比之下，随着年龄的增长，人体逼尿肌平滑肌nNOS组织化学染色和EFS诱导的NO释放明显减少。AGE的形成与NO的释放呈负相关。脊髓损伤大鼠与对照大鼠相比，EFS诱导的NO释放明显减少，膀胱AGE形成明显增加。提示在生理和病理生理条件下，AGE的形成与膀胱功能NO释放/NOS活性有显著关系。但其与膀胱功能关系的机制有待进一步研究。少

Nitric oxide (NO) is one of the most important molecules for regulation of lower urinary tract function in the physiological and pathophysiological conditions. Furthermore, it has been demonstrated that advanced glycation end products (AGE) contributes to damages of the cellular function through the AGE-receptors in various tissues. In this study, we have evaluated the role of NO and AGE on bladder function.In rat and human detrusor specimens, NADPH-diaphorase staining and nNOS immunohistochemical staining showed the NADPH-positive and nNOS-positive neurons, which are significantly less as compared to urethral and prostatic specimensIn the functional experiments, electrical field stimulation (EFS) did not cause significant relaxation responses in smooth muscle strips isolated from human and rabbit bladder precontracted with carbachol. However, L-NNA (a NOS inhibitor) caused a significant increase in EFS-induced acetylcholine (ACh) release from cholinergic nerve endings in the rabbit bl … More adder. The data suggest that NO has an inhibitory action on ACh release in bladder, which may cause increase in bladder capacity and decrease in detrusor instability in the filling phase of micturition cycle.There were AGE formations in human detrusor specimens. The formation was significantly higher in the aged patients, and there was significant positive correlation between age and AGE formation. In contrast, nNOS histochemical staining and NO release induced by EFS in human detrusor smooth muscles were significantly decreased with age. And, there was a negative correlation between AGE formation and NO release. In rats with spinal cord injury, NO release induced by EFS was significantly decreased, and AGE formation was significantly increased in the bladder, as compared to bladder of the control rat.The data may suggest that there was significant relationship between AGE formation and NO release/NOS activity in bladder function in physiological and pathophysiological conditions. However, further studies are needed to evaluate the mechanism of the relationship for bladder function. Less