Modulation of NO production by arginase in the rabbit lower urinary tract

Objective: We examined whether endogenous arginase is expressed and can play a functional role in regulating neurogenic and NO-mediated relaxation in the rabbit lower urinary tract. Methods: Strips of detrusor, trigone, proximal urethra and prostate obtained from Japanese white male rabbits weighing approximately 3. 0Kg were processed for organ bath studies and arginase activity. Results: Electrical field stimulation (EFS) induced nonadrenergic and noncholinergic (NANC) nerve- mediated relaxation in the trigone, proximal urethra and prostate, while no relaxation response was observed in the detrusor. These relaxations were inhibited by NG-nitro-L- arginine (L-NOARG) as a NOS inhibitor and enhanced by N-hydroxy-L-arginine (NOHA) as an arginase inhibitor in a concentration-dependent manner. The inhibition with L- NOARG was reversed by NOHA as well as L-arginine. The rank order of arginase activity was prostate, urethra, trigone and detrusorIn all regions, 100μM NOHA caused approximately 95% inhibition of arginase activity, while the L-NOARG (100μM) had no effect. Conclusion: These results indicate that the endogenous arginase plays a counteracting role in modulating NOS activity in lower urinary tract.