Correlation of Functional Changes on Bladder and Proximal Urethra with Neuronal Nitric Oxide Synthase in Pelvic Ganglion Denervated Rats

Kim, Je Wook; Jung, Hee Chang; Park, Tong Choon

Abstract

Injuries to the pelvic nerve plexus following major pelvic ablative surgery are commonly observed conditions in urologic field and often related to voiding difficulty with flaccid type of neurogenic bladder. The pathophysiological background for voiding difficulty is unknown and also it is difficult to investigate in human. The present study was undertaken to investigate the functional changes on the bladder and urethra in major pelvic ganglion denervated rats (experimental group). Injury to the pelvic nerve plexus was created by selective removal of bilateral major pelvic ganglions of mature Sprague-Dawley rats (male, 250-300 gm). One week after operation, urodynamic evaluation and NADPH diaphorase histochemistry were performed in each rat. The whole bladder wet weight and residual urine of experimental group significantly increased to 1.6 times and 29 times that of control group, respectively. For urodynamic investigations, the bladder and the urethra were completely disconnected by means of ligation between the bladder neck and the proximal urethra, and simultaneous recordings of the intravesical and proximal urethral pressure were performed. During simultaneous urethro-vesical filling in experimental group, vesical contraction and urethral relaxation were not induced. However, an administration of L-arginine (120 mg/kg intravenously), a nitric oxide substrate, resulted in a gradual decrease in urethral pressure when the bladder pressure was reached at submaximal level. On NADPH diaphorase histochemistry in control group, a large number of NADPH positive nerve fibers were found in the proximal urethra, whereas those were found less commonly in the bladder. In experimental group, the number of NOS positive nerve fibers in the bladder was similar to that in control group. But in the proximal urethra, the number of NOS positive nerve fibers (84.7 +/- 12.7) decreased significantly in contrast to that (185.9 +/- 56.3) in control group. These results indicate that failure to empty in neurogenic bladder may be resulted from relaxation impairment of bladder outlet, which can be explained by the reduction of neuronal NOS in the proximal urethra in experimental group.