Neuroanatomical changes in the rat bladder after bladder outlet obstruction

Objective To investigate the histological changes in bladder innervation in response to partial bladder outlet obstruction in a rat model. Materials and methods Forty‐eight adult female rats had their bladder outlet partially obstructed by ligating the proximal urethra over a 20 G angiocatheter; 18 sham‐operated rats served as controls. Animals were killed after 1, 2 and 4 weeks, and their bladders evaluated using computerized morphometry. Immunohistochemical staining for neuronal protein gene‐product 9.5 (PGP, a general neuronal marker) and enzyme histochemical staining of acetylcholinesterase, adrenergic fibres and nitric oxide synthase were performed. Results Bladder wall changes after obstruction consisted of a six‐ to sevenfold increase in bladder volume and weight. Smooth muscle hypertrophy was evident equally at all sample times. Cystometry showed functional alterations in bladder capacity and voided pressures; obstructed animals had markedly increased bladder capacities and higher voiding pressures (obstructed, 80–100 cmH2O; normal, 30–40 cmH2O). Neuronal changes in the obstructed bladder were most dramatic within the cholinergic and adrenergic neurotransmitter systems within and surrounding the smooth muscle bundles, where there was less staining than in control animals. PGP immunoreactivity increased slightly. The l‐arginine‐nitric oxide pathway appeared unperturbed after obstruction. Conclusions These histological findings suggest that neuropathic changes in the bladder after outlet obstruction, including detrusor instability, are mainly the result of anatomical perturbations in the cholinergic and adrenergic pathways.