ROLE OF SPINAL NITRIC-OXIDE IN THE FACILITATION OF THE MICTURITION REFLEX BY BLADDER IRRITATION

Purpose: Nitric oxide (NO) is known to have an important transmitter f unction at peripheral synapses in the urogenital tract and has also be en implicated in the transmission of nociceptive information in the sp inal cord. The present study evaluated the role of NO in the central m icturition reflex pathway. Materials and Methods: We examined the effe ct of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO syn thase, on micturition reflexes induced by continuous infusion of salin e or 0.1% acetic acid (a noxious stimulus) into the bladder in urethan e-anesthetized female rats. Bladder and external urethral sphincter fu nction were monitored with a continuous cystometrogram (CMG) and elect romyography (EMG). Results: Intrathecal injection of L-NAME (0.01 to 1 mu mol.) did not significantly change the CMG or sphincter EMG during saline infusion. Infusion of acetic acid decreased the intercontracti on interval (ICI), indicating a decrease in the volume threshold for i nducing micturition. Subsequent intrathecal administration of L-NAME p artially reversed the decreased ICI in a dose-dependent manner, but di d not change the amplitude of bladder contractions: 0.01, 0.1 and 1 mu mol. of L-NAME produced increases of 25%, 31% and 56% in the ICI. D-N AME, the inactive stereoisomer had no effect. This effect of L-NAME wa s reversed by injection of L-arginine (2 b mu mol. intrathecally) whic h, by itself, did not alter ICI during saline infusion or acetic acid infusion. Conclusions: These results indicate that: (1) spinal NO cont aining pathways do not play a role in the normal micturition reflex, ( 2) NO is involved at the spinal level in the facilitation of the mictu rition reflex by nociceptive bladder afferents activated by noxious ch emical irritation of the bladder.