Roles of brain nitric oxide in micturition of rats

抄録

Background: Peripheral nitric oxide (NO) has a local inhibitory effect on urination, while, in the central nervous system, NO seems to have both inhibitory and facilitatory effects. We previously reported that SIN-1 (NO donor) centrally activated the sympatho-adrenomedullary (SA) system in rats. In this study, we investigated effects of centrally administered SIN-1 on micturition and their dependence on the SA system in rats.

Methods: Urethane-anesthetized (0.8 g/kg, ip) male Wistar rats (300-400 g) were used. (1) Catheters were inserted into the bladder and the femoral artery in order to measure intravesical pressure and to collect blood samples, respectively. SIN-1 (100 or 250 µg/rat) or vehicle was intracerebroventricularly (icv) administered. One hour before the administration, continuous intravesical instillation of sterile saline (12 ml/h) and measurement of intravesical pressure were started. Plasma noradrenaline and adrenaline levels were measured at 5 min after the administration. In some experiments, carboxy-PTIO (NO scavenger, 750 µg/rat, icv) was pretreated 30 min before SIN-1 administration (250 µg/rat, icv). (2) Single cystometry was performed in rats inserted a catheter into the bladder. Saline instillation (12 ml/h) was continued until the peak of a voiding bladder contraction; then the instillation was stopped and the saline voided from the bladder was collected and measured (single-voided volume, Vv). The bladder was then emptied to measure residual volume (post-voiding residual urine volume, Rv). This procedure was performed 4-5 times before SIN-1 administration (250 µg/rat, icv), and performed from 0 to 60 min after the administration. After experiments, bladder capacity (BC = Vv + Rv) and voiding efficiency (VE = Vv/BC) were calculated.

Results: (1) SIN-1 dose-dependently reduced intercontraction intervals (ICI) and elevated plasma adrenaline without altering maximal voiding pressure or plasma noradrenaline. An insufficient dose of SIN-1 (100 µg/rat) for elevating plasma adrenaline could induce ICI reduction. Carboxy-PTIO attenuated these SIN-1-induced responses. (2) SIN-1 reduced Vv and BC without altering Rv or VE.

Conclusions: NO centrally induces frequent urination shown by reduced ICI, Vv and BC, independent of the central SA outflow. Thus, the brain nitrergic pathway that can directly regulate micturition might be a potential therapeutic target for bladder dysfunction.