Response and mast cell activation to tolterodine in protamine sulfate‐ and lipopolysaccaride‐treated rat urinary bladder (865.9)

Abstract

We aimed to use an animal model of chronic interstitial cystitis in rats to investigate the histology and function of the bladder, with a special focus on mast cell degranulation and response of detrusor overactivity to tolterodine. A total of 18 female Sprague‐Dawley rats were used in this study. In 12 rats, lipopolysaccharide was intravesically instilled after the induction of interstitial cystitis by protamine sulfate; 6 rats were subjected to sham instillations. After 1 month, cystometry was performed in all rats with simultaneous registrations of intravesical and intraabdominal pressures. The effects of tolterodine on bladder function were tested in half of the interstitial cystitis animals. All rats in the interstitial cystitis group showed detrusor overactivity during the filling phase and no significant changes in frequency or pressure compared with that after tolterodine injection. Histological examination revealed a significant increase in total numbers of infiltrated mast cells in the interstitial cystitis rats compared with the sham rats (p<0.05). Eighty percent of the interstitial cystitis rats showed degranulated mast cells, whereas the sham rats did not. Urinary bladder inflammation similar to that in human interstitial cystitis in terms of degranulated mast cells and bladder function was induced in Sprague‐Dawley rats. Our animal model should provide major insights into pathophysiologic mechanisms in the bladder, such as the mechanisms underlying the ineffectiveness of anticholinergics in patients with overlapping interstitial cystitis and overactive bladder.