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 outle t partially obstructed by ligating the proximal urethra over a 20 G angioca theter; 18 sham-operated rats served as controls. Animals were killed after 1, 2 and 4 weeks. and their bladders evaluated using computerized morphome try. Immunohistochemical staining for neuronal protein gene-product 9.5 (PG P, a general neuronal marker) and enzyme histochemical staining of acetylch olinesterase, adrenergic fibres and nitric oxide synthase were performed. Results Bladder wall changes after obstruction consisted of a six- to seven fold increase in bladder volume and weight. Smooth muscle hypertrophy was e vident equally at all sample times, Cystometry showed functional alteration s in bladder capacity and voided pressures; obstructed animals had markedly increased bladder capacities and higher voiding pressures (obstructed, 80- 100 cmH(2)O; normal, 30-40cmH(2)O), Neuronal changes in the obstructed blad der were most dramatic within the cholinergic and adrenergic neurotransmitt er systems within and surrounding the smooth muscle bundles, where there wa s less staining than in control animals. PGP immunoreactivity increased sli ghtly. The L-arginine-nitric oxide pathway appeared unperturbed after obstr uction, 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 adrene rgic pathways.