Oxytocin-induced stimulation and inhibition of bladder activity in normal, conscious rats--influence of nitric oxide synthase inhibition.

The role of the oxytocin-containing projections to the autonomic nuclei of the spinal cord for lower urinary tract function has not been clarified. The hypothesis was tested that oxytocin acts as a mediator of bladder contraction at the spinal cord level. In conscious female rats undergoing continuous cystometry, intrathecal oxytocin (30 ng approximately 30 pmoles) significantly increased micturition pressure (P<0.001), and decreased bladder capacity (P<0.01) and micturition volume (P<0.01). Residual volume increased (P<0.05), and so did the amplitude and frequency of non-voiding contractions (P<0.01). Immediately after administration of oxytocin, the animals showed frequent stretching movements and yawning, and they licked their tails. The effects of oxytocin were dose-dependent; high concentrations (100 ng) were ineffective. Intra-arterial injection of oxytocin (30 ng) near the bladder had no effect. In isolated detrusor strips, oxytocin caused a concentration-dependent contraction; the concentration response curve was concentration-dependently shifted to the right by the oxytocin antagonist, 1-deamino, 2-D-Tyr(OEt), 4-Thr, 8-Orn-OT. Intrathecal injection of the antagonist (500 ng), had per se no effect on micturition. However, when the antagonist was given intrathecally 4-5 min prior to intrathecal oxytocin (30 ng), the effects of oxytocin were reduced or completely prevented. When given after intrathecal administration of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, intrathecal oxytocin (30 ng) abolished micturition within 5-7 min; all animals developed overflow incontinence, and paralysis of the hindlimbs. These results suggests that in the rat, oxytocin, released from descending pathways, may act as a modulator of the micturition reflex at the spinal level, and that it may interact with nitric oxide. The physiological implications of the findings remain to be established.