光応答性NOドナー「NORD-1」の下部尿路機能障害に対する応用

抄録

Objective Nitric oxide (NO) is an essential neurotransmitter in the lower urinary tract (LUT). Since it is known that NO deficiency leads to LUT dysfunction (LUTD), supplementary of NO might be an effective therapy for LUTD. However, there are some issues in the biological application of NO. Firstly, it is difficult to control the timing of NO action, because of its short half-life and rapid diffusion. Secondly, NO leads to systemic side effects such as headache or hypotension. To resolve these issues, we developed a red-light reactive NO donor, “NORD-1,” with which we could regulate the release of NO temporally and spatially. In this study, we aimed to examine the possibility to apply NORD-1 to LUTD.

Methods We used 10-11-week-old Wistar/ST rats. We injected NORD-1 or vehicle into the rats’ bladder and used those rats for the experiments after twenty minutes. As in vitro study, we performed the isometric tension study on the bladder neck and bladder body specimens. Also, we performed cystometry to evaluate the function of the bladder as in vivo study.

Results The specimens of the vehicle group did not react to the light irradiation. The bladder neck specimen of the NORD-1 group was relaxed during light irradiation. In contrast, the bladder body specimen of the NORD-1 group did not react to the light irradiation. On the cystometry, the micturition intervals were prolonged during the irradiation.

Conclusion We succeeded to control both the bladder neck relaxation and the micturition of rats using NORD-1 and red-light irradiation. NORD-1 may be a novel therapeutic agent for LUTD.