Neural control of urethral outlet activity in vivo: role of nitric oxide.
The present study investigated the role of nitric oxide (NO) in the reflex changes in urethral outlet activity during micturition. Isovolumetric bladder contractions, urethral pressure and external urethral sphincter electromyogram (EUS EMG) activity were recorded independently in urethane-anesthetized rats. During reflex bladder contractions, the urethra exhibited reflex responses characterized by an initial decrease in urethral pressure in conjunction with a rise in bladder pressure. This was followed by a period of high frequency oscillations (HFOs) associated with maximal urethral relaxation and burst type EUS EMG activity. Administration of N-nitro-L-arginine (L-NOARG) 10 mg./kg. intravenously, a nitric oxide synthase inhibitor, reversibly decreased the magnitude (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). Administration of N-nitro-D-arginine (D-NOARG) (10 to 30 mg./kg. intravenously) had no effect on reflex urethral relaxation. Neuromuscular blockade (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 eliminated following administration of L-NOARG (10 mg./kg. intravenously) in 2 of 3 animals. These results suggest that reflex urethral responses during micturition involve changes in both smooth and striated muscle activity, and that the predominant neurotransmitter mechanisms that mediate reflex urethral smooth muscle relaxation involve NO.
Bennett, BC; Kruse, MN; Roppolo, JR; Flood, HD; Fraser, M; de Groat, WC
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