Distribution and regional variation of pituitary adenylate cyclase activating polypeptide and other neuropeptides in the rat urinary bladder and ureter: effects of age.

The distribution and regional variation of nerves immunoreactive for the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide were investigated in the urinary bladder and distal ureter of young adult (3 months) and aged (24 months) male Wistar rats by indirect immunohistochemistry. Semi-quantitative estimations of nerve densities were made of peptidergic fibres innervating the dome, body and base of the urinary bladder and distal ureter. Sensory innervation of the dome was very sparse and the overall density of innervation increased progressively towards the base of the bladder. The density of innervation in the aged rats was closely comparable to that in the young adults, with the exception of slight reductions in CGRP and SP innervation of the muscle layer. Moreover, there was a marked reduction in the density of PACAP innervation of the subepithelial plexus and of the muscle layer of the bladder base. However, radioimmunoassay showed no significant difference (P>0.05) in PACAP contents between young and aged rat urinary bladder. In the distal ureter of aged rats the densities of innervation by fibres immunoreactive for SP and PACAP but not CGRP were reduced. These findings suggest that the level of sensory innervation of the bladder and distal ureter are reduced in old age and that the afferent limb of voiding reflexes may in consequence be perturbed.