INVESTIGATIVE UROLOGY

The distribution of neuronal and inducible nitric oxide synthase in urethral stricture formation
Cavalcanti AG, Yucel S, Deng DY, McAninch JW, Baskin LS
Department of Urology and Pediatrics, University of California-San Francisco Children’s Medical Center, University of California-San Francisco, USA
J Urol. 2004; 171: 1943-7

• Purpose: The distribution of neuronal (n) and inducible (i) nitric oxide synthase (NOS) may have a role in the maintenance of normal urethral spongiosum and during the development of spongiofibrosis in urethral stricture disease.
• Materials and Methods: Eight normal and 33 strictured human bulbar urethras were studied by histological and immunohistochemical techniques for the neuronal markers S-100, nNOS and iNOS. The smooth muscle-to-collagen ratio was calculated by morphometric analysis of Masson’s trichrome sections. Immunohistochemical staining patterns of the neuronal markers in normal urethral tissue was compared to that in urethral stricture tissue with spongiofibrosis.
• Results: The smooth muscle-to-collagen ratio was significantly lower in the strictured urethra compared to that in the control group (p = 0.001). In the strictured bulbar urethra nNOS immunoreactivity was decreased compared to that in normal urethral tissue. The severity of spongiofibrosis corresponded to the loss of nNOS immunoreactivity. iNOS immunoreactivity was found in strictured urethral epithelium and spongiosal tissue, whereas the control group was nonimmunoreactive to iNOS.
• Conclusions: Urethral stricture formation is a fibrotic process associated with significant changes in NOS metabolism. Abnormal collagen synthesis following urethral trauma may be stimulated by inappropriate iNOS activity. A functional nerve supply to the urethral spongiosum seems to be crucial in the maintenance of the unique ultrastructure of the urethral spongiosum.
  
  
• Editorial Comment
  It is well known that in the strictured urethra the main changes are found in the extracellular matrix. As well as in other tissues, the normal urethra and spongiosal tissue must have an adequate blood supply and nerve innervation to maintain its elastic and compliant characteristics. To our knowledge, this is the first study to analyze the quality of the nerve supply of the urethral spongiosum in the normal and strictured urethra. The authors investigated the changes of neuronal and inducible nitric oxide synthase (NOS) immunoreactivity in strictured bulbar urethras with different degrees of spongiofibrosis.
  Structural differences in spongiosal tissue were described previously stating that biomechanical properties required for normal urethral function differ in the spongiosal tissue of glanular, penile and bulbar segments. For this study, the authors consistently used the bulbar urethra in the stricture and control groups.
  The authors found a decrease in neuronal NOS activity associated with a slight increase in inducible NOS activity and postulated that it could result in a decrease in total NOS activity, leading to abnormal collagen synthesis. They concluded that urethral stricture formation is a fibrotic process associated with significant molecular changes in NOS metabolism. Also, they found that a functional nerve supply to the urethral spongiosum seems to be crucial in the maintenance of the urethral spongiosum structure.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil