Nonadrenergic, noncholinergic inhibitory control of the rat external urethral sphincter: involvement of nitric oxide

Administration of norepinephrine (0.1 mM) to the isolated rat external urethral sphincter (EUS) produced a tonic contraction which was inhibited by phentolamine (3 microM), but not by tetrodotoxin (0.6 microM). Electrical field stimulation (EFS; 60 V, 1 msec, trains of 5 sec every 5 min) of the EUS, performed after norepinephrine-induced urethral contractions had reached steady state, resulted in a frequency-dependent (1.5-5 Hz) relaxation. EFS-induced relaxation was abolished by tetrodotoxin (0.6 microM); and it was diminished or abolished in samples taken from rats in which the pudendal nerves and/or the major pelvic ganglia or the lumbosacral spinal cord had been cut or removed 10 days before. Propranolol (3 microM), atropine (3 microM), indomethacin (5 microM) or hexamethonium (10 microM) did not affect EFS-induced relaxation. Preincubation with L-NG-nitro-arginine (L-NOARG), however, inhibited the EFS-induced relaxation in a concentration-dependent manner (10-100 microM). The effect of L-NOARG (50 microM) was reversed by L-arginine (300 microM), but not by D-arginine (300 microM). EFS (2.5 Hz, 60 V, 1 msec, trains of 5 sec every 5 min) of the resting EUS, produced a tetrodotoxin-sensitive response with a tonic contraction component, which was inhibited by phentolamine but, in contrast, was enhanced by L-NOARG (100 microM). Altogether, these findings indicate that the inhibitory nonadrenergic, noncholinergic pathways that innervate the EUS in rats travel mostly with the pudendal nerves. This neural inhibitory system may act via the synthesis and release of nitric oxide or a nitric acid-containing compound.