Alterations in cholinergic and neuropeptide innervation of urinary bladder following partial bladder outlet obstruction.

Posterior urethral valves (PUV) are the most common cause of bladder outlet obstruction (BOO) in infancy. Bladder instability, poor compliance and myogenic failure are responsible for the poor long-term prognosis in these patients. Previous studies have reported abundance of sensory neuropeptides, e.g. substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and acetylcholinesterase (AchE) nerves in the urinary bladder. We hypothesized that the functional changes in the bladder following BOO are due to alteration in cholinergic and sensory neuropeptide innervation. We therefore investigated cholinergic and sensory innervation of urinary bladder following BOO. Fifteen immature male guinea pigs (Hartley strain) 3-4 weeks old and weighing approximately 250 g. underwent placement of a silk ligature around the bladder neck to induce BOO. Controls included 5 sham-operated animals. The animals were killed 1, 2 and 4 weeks following obstruction, respectively. Whole-mount preparation and conventional sections of bladder wall were performed. AchE histochemistry, and single-label immunofluorescence histochemistry for SP, CGRP and VIP were utilized. Light microscopy and laser scanning confocal microscopy were used to assess the results. AchE staining showed marked increase in cholinergic innervation density within the suburothelial region following BOO. The staining for SP, CGRP and VIP demonstrated marked reduction in sensory nerve density within the suburothelial region 1 week following BOO and the lack of sensory innervation 4 weeks after BOO. The marked reduction in sensory innervation of the bladder and simultaneous increase in cholinergic innervation following BOO may lead to bladder instability and decrease in bladder compliance.