Effects of Nitric Oxide on the Primary Bladder Afferent Activities of the Rat With and Without Intravesical Acrolein Treatment

Background: It has been suggested that nitric oxide (NO) affects the afferent pathways innervating the bladder. In addition, acrolein, a metabolite of cyclophosphamide, causes bladder hypersensitivity in rats. Objective: We investigated the direct effects of an NO substrate (L-arginine) and an NO synthase inhibitor (N-omega-nitro-L-arginine methyl ester hydrochloride [L-NAME]) on single fiber activities of the primary bladder afferent nerves with or without acrolein application. Design, setting, and participants: Female Sprague-Dawley rats were used. Under urethane anesthesia, a single nerve fiber primarily originating from the bladder was identified by electrical stimulation of the left pelvic nerve and by bladder distention, and it was divided by conduction velocity as A delta fiber or C fiber. Measurements: The afferent activity measurements with constant bladder filling were repeated three times, and the third measurement served as the baseline observation. After that, two experiments were performed. First, L-NAME (10 mg/ml) was instilled intravesically. Then L-arginine (300 mg/kg) was administrated intravenously to investigate the competition with L-NAME. Second, L-arginine was administrated intravenously. Then 0.003% of acrolein or saline was instilled intravesically to obtain another three cycles of instillations. Results and limitations: Forty-two single afferent fibers (A delta fibers: n = 19; C fibers: n = 23) were isolated in 31 rats. When the bladder was filled with L-NAME solution, afferent activities of both A delta and C fibers increased significantly, and L-arginine administration inhibited these stimulated responses. In addition, intravenous administration of L-arginine significantly decreased the activities of both fibers during saline instillation. Intravesical acrolein instillation significantly increased the activities of both fibers, which were inhibited by pretreatment with L-arginine. Conclusions: The results suggest that NO synthase exists in the rat urinary bladder and clearly demonstrate that L-arginine, an NO substrate, can inhibit both A delta and C mechanosensitive afferent fibers of the bladder in the rat. In addition, L-arginine can inhibit the activated responses of both fibers to intravesical acrolein. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.