Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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Research Abstract |
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 specimens In 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
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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
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