Submitted on October 29, 2007
Accepted on June 9, 2008
Long-lasting breaches in the bladder epithelium lead to storage dysfunction with increase in bladder PGE2 levels in the rat
Rikiya Shioyama1, Yoshitaka Aoki1, Hideaki Ito2, Yosuke Matsuta3, Keiko Nagase2, Nobuyuki Oyama2, Yoshiji Miwa2, Hironobu Akino2, Yoshiaki Imamura4, and Osamu Yokoyama2*
1 Urology, University of Fukui, Eiheiji, Fukui, Japan
2 Eiheiji, Fukui, Japan; Urology, University of Fukui, Eiheiji, Fukui, Japan
3 Urology, University of Fukui, Eiheiji, Fukui, Japan; Eiheiji, Fukui, Japan
4 Division of Surgical Pathology, University of Fukui, Eiheiji, Fukui, Japan
* To whom correspondence should be addressed. E-mail: oyoko{at}u-fukui.ac.jp.
Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wister rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 weeks. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The 5th group of rats received a high dose (10 mg/ml) PS for 2 weeks and were followed for a further 2 weeks without PS. The 6th group received a high dose PS for 2 weeks and loxoprofen (0.1 mg/kg/day) for 4 weeks. UF was increased and VV was reduced in rats treated with a high dose PS, but not changed in rats treated with a vehicle or a low dose (1 mg/ml) PS. UF was further increased in the 5th group, while unchanged in the 6th group. Histological sections in rats treated with a high dose PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the 5th group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.
