NEURAL CONTROL OF URETHRAL OUTLET ACTIVITY IN-VIVO - ROLE OF NITRIC-OXIDE

The present study investigated the role of nitric oxide (NO) in the re flex changes in urethral outlet activity during micturition. Isovolume tric bladder contractions, urethral pressure and external urethral sph incter electromyogram (EUS EMG) activity were recorded independently i n urethane-anesthetized rats. During reflex bladder contractions, the urethra exhibited reflex responses characterized by an initial decreas e in urethral pressure in conjunction with a rise in bladder pressure. This was followed by a period of high frequency oscillations (HFOs) a ssociated with maximal urethral relaxation and burst type EUS EMG acti vity. Administration of N-nitro-L-arginine (L-NOARG) 10 mg./kg. intrav enously, a nitric oxide synthase inhibitor, reversibly decreased the m agnitude (62%, p <0.05) and duration (40%, p <0.05) of reflex urethral relaxation (N = 7). In 4 additional experiments, L-NOARG (10 to 15 mg ./kg. intravenously) completely eliminated reflex urethral relaxation during micturition, and this effect was reversed in all animals by the administration of L-arginine (100 to 150 mg./kg. intravenously). Admi nistration of N-nitro-D-arginine (D-NOARG) (10 to 30 mg./kg. intraveno usly) had no effect on reflex urethral relaxation. Neuromuscular block ade (vecuronium bromide 5 mg./kg. intravenously) reversibly decreased resting urethral pressure and eliminated the HFOs. The urethral smooth muscle relaxation that remained after neuromuscular blockade was elim inated following administration of L-NOARG (10 mg./kg. intravenously) in 2 of 3 animals. These results suggest that reflex urethral response s during micturition involve changes in both smooth and striated muscl e activity, and that the predominant neurotransmitter mechanisms that mediate reflex urethral smooth muscle relaxation involve NO.