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

Abstract

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,intrathecaloxytocin (30 ng ≈ 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 ω-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.