Effects of nitric oxide on the primary bladder afferent activities of the rat with and without intravesical acrolein treatment.

Abstract

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. We investigated the direct effects of an NO substrate (L-arginine) and an NO synthase inhibitor (N(ω)-nitro-L-arginine methyl ester hydrochloride [L-NAME]) on single fiber activities of the primary bladder afferent nerves with or without acrolein application. 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 Aδ fiber or C fiber. 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 (10mg/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. Forty-two single afferent fibers (Aδ 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 Aδ 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. The results suggest that NO synthase exists in the rat urinary bladder and clearly demonstrate that L-arginine, an NO substrate, can inhibit both Aδ 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.