Inducible nitric oxide synthase in the bladder of spinal cord injured patients with a chronic indwelling urinary catheter

Purpose: Spinal cord injured patients are at increased risk for bladder car cinoma. Nitric oxide production in areas of chronic inflammation may provid e a stimulus for carcinogenesis by serving as a source of nitrosating agent s that generate potentially carcinogenic nitrosamines from secondary amines normally present in urine. Materials and Methods: To determine whether inducible nitric oxide synthase is expressed as a catalyst for sustained nitric oxide production by cellul ar elements in chronically inflamed bladder mucosa immunohistochemical stud ies were performed on mucosal biopsies obtained from 37 adults with spinal cord injury. All participants had required a chronic indwelling urethral or suprapubic catheter for greater than 8 years. Results: Histopathological studies revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous metaplasia in 20, epithelial dysplasi a in 3 and carcinoma in 1. Inducible nitric oxide synthase was detected in inflammatory cells localized to the lamina propria. Inducible nitric oxide synthase positive cells were identified as macrophages using monoclonal ant ibodies to macrophage antigen. There was no inducible nitric oxide synthase expression in the urothelial cell layers. Immunostaining for inducible nit ric oxide synthase was not detected in bladder mucosal biopsy specimens obt ained from cadaveric organ donors. Conclusions: Inducible nitric oxide synthase is expressed in inflammatory m acrophages in areas of chronic inflammation in the bladder mucosa of spinal cord injured patients with a chronic indwelling bladder catheter. The expr ession of inducible nitric oxide synthase may potentially lead to the susta ined production of nitric oxide and its oxidative products, the nitrosation of urinary amines and the formation of potentially carcinogenic nitrosamin es in the bladder.