The use of Hypochlorous Acid as a Model for Investigating Bladder Overactivity

Involuntary detrusor contractions play an important role in the development of urge incontinence. Also in an in-vitro situation contractions which develop spontaneously can be seen; a parallel with the in vivo observations is likely. In order to study this muscle overactivity we investigated the possibility to induce this phenomenon with oxidative stress using hypochlorous acid (HOCl). Materials and Methods: Urinary bladder muscle strips from pigs were mounted in a custom made organ bath and incubated for 20 minutes in Krebs solution. Next HOCl (10 mu M) was added to the organ bath and the onset of overactive contractions was closely followed. Overactivity was defined as a development of more than 5 phasic detrusor contractions per minute without any other provocation in the 30 minutes following addition of HOCl to the organ bath. Results: Of the 50 strips which were used 36 (72%) became overactive after exposure to HOCl during 30 minutes recording. In 76% of the overactive strips overactivity occurred within 5 minutes, in 19% between 5 and 15 minutes, and in 5% it took longer than 15 minutes. The overactivity could be stopped by washing out HOCl for 10 minutes after which still a significant contraction after EFS and ACh stimulation was seen. Conclusions: It can be concluded that an oxidative stressor, like HOCl, is capable of inducing smooth muscle overactivity. This model can be used for the development and testing of new treatment modalities for the overactive detrusor. Furthermore, this study provides evidence for a causal relationship between oxidative stress and detrusor overactivity.