Presentation Authors: Masahiro Kurobe*, Pittsburgh, PA, Ei-ichiro Takaoka, Narita, Japan, Takahisa Suzuki, Hamamatsu, Japan, Shinsuke Mizoguchi, Tetsuichi Saito, Pittsburgh, PA, Jun Miyazaki, Narita, Japan, Hiroyuki Nishiyama, Tsukuba, Japan, Edwin K. Jackson, Lori A. Birder, Naoki Yoshimura, Pittsburgh, PA
Introduction: Previous studies on bladder outlet obstruction (BOO)-induced bladder dysfunction often utilized female rats. Also, recent studies using female rats have reported that adenosine receptor (AR) modulation can affect bladder function. However, the AR mechanism underlying BOO-related bladder dysfunction is not well elucidated, especially in male rats. Thus we examined the expression of AR subtypes after BOO, and the effects of adenosine A2B receptor (A2B-R) deletion on bladder activity using male rats.
Methods: BOO was induced in male Sprague-Dawley rats by partial ligation of the proximal urethra. At 4 weeks after BOO, conscious cystometrograms (CMG) were performed with the urethral ligature intact. Sham operated animals were used as controls. mRNA levels of AR subtypes such as A1, A2A, A2B and A3 in bladder mucosa and detrusor layers were analyzed by RT-PCR. Furthermore, we examined the difference of bladder function between A2B-R knockout (A2BKO) and wild-type (WT) groups of male Dahl salt-sensitive rats by CMG.
Results: Bladder weight of BOO rats was significantly increased compared to sham rats. In CMG, BOO rats exhibited significant increases in contraction amplitudes, non-voiding contractions (NVC), post-void residual, bladder capacity, and compliance compared to sham rats (Fig.1A,B). Voiding efficiency (VE) was decreased in BOO rats vs. sham rats. mRNA expression levels of A2A and A3 were significantly increased, and A2B levels were significantly decreased in bladder mucosa, but not in detrusor, of BOO rats vs. controls (Fig.1C). In comparison of A2BKO and WT rats, the NVC number was significantly increased in A2BKO rats compared to WT (Fig.2A,B).
Conclusions: These results indicate that BOO-induced bladder overactivity evident as NVC increase was associated with the reduced mucosal expression of A2B-R, and the A2B-R deletion led to bladder overactivity in male rats. Therefore, the reduction of A2B-R could be an important mechanism for the development of bladder overactivity due to BOO in male BPH patients.
Source of Funding: NIH U54DK112079