Presentation Authors: Takahiro Shimizu*, Yohei Shimizu, Hideaki Ono, Suo Zou, Masaki Yamamoto, Shogo Shimizu, Youichirou Higashi, Takaaki Aratake, Tomoya Hamada, Yoshiki Nagao, Yusuke Ueba, Nankoku, Japan, Masashi Honda, Yonago, Japan, Motoaki Saito, Nankoku, Japan
Introduction: Psychological stress exacerbates symptoms of bladder dysfunction. We previously reported that epibatidine (EP), a nicotinic acetylcholine receptor (nAChR) agonist, centrally activated a representative response to stress, the sympatho-adrenomedullary (SA) system, in rats. In this study, we examined effects of centrally administered EP on micturition reflex and their dependence on the SA system in rats.
Methods: Urethane anesthetized (0.8 g/kg, ip) male Wistar rats (350-450 g) were used. (1) Catheters were inserted into the bladder and the femoral artery to perform cystometrograms (CMG, 12 ml/h saline infusion) and to collect blood samples, respectively. Three hours after the surgery, EP (0.3 or 1 nmol/rat) or vehicle was icv administered. CMG was started 1 hour before the icv administration. Plasma noradrenaline (NA) and adrenaline (Ad) were measured at 5 min after the icv administration. In some rats, acute bilateral adrenalectomy (ADX) was performed before the insertion. (2) Catheters were inserted into the bladder and the femoral vein to perform CMG and to administer EP (1 nmol/rat, iv), respectively. CMG was performed as described in (1). (3) Effects of icv pretreated mecamylamine (MEC, 100 or 300 nmol/rat), a nAChR antagonist, on the EP (1 nmol/rat, icv)-induced responses were examined.
Results: (1) Icv administered EP dose-dependently prolonged intercontraction intervals (ICI) and elevated plasma NA and Ad without altering maximal voiding pressure (Table 1, Fig. 1). ADX almost abolished the EP-induced elevation of both NA and Ad without affecting the ICI prolongation (Table 2). (2) Iv administered EP showed no significant effect on ICI (data not shown). (3) MEC dose-dependently attenuated the EP-induced ICI prolongation (Fig. 2) and elevation of NA and Ad (data not shown).
Conclusions: Activation of brain nAChRs might suppress micturition reflex, independent of the SA outflow modulation. Thus, brain nAChRs could be a new target for the treatment of stress-induced bladder dysfunction.
Source of Funding: Smoking Research Foundation in Japan, JSPS KAKENHI (#17K09303), Takeda Science Foundation