Effects of the light-controlled nitric oxide donor “NORD-1” and light irradiation in rats with neurogenic erectile dysfunction

ABSTRACT Introduction Radical prostatectomy often causes erectile dysfunction (ED). This is considered to be due to surgery-induced nerve damage. Impairments in neurotransmission result in the release of nitric oxide (NO) in penile corpus cavernosum insufficiency. Therefore, phosphodiesterase-5 inhibitors are not necessarily effective for this type of ED. NO supplementation may be effective for this type of ED. However, NO acts on the whole body and thus may cause adverse effects. Recently, we have developed a light-controlled NO donor that enables spatially and temporally controlled NO release by light irradiation. Whether this type of NO donor is useful for neurogenic ED remains unknown. Objective We investigated whether this light-controlled NO donor “NORD-1” and light irradiation were effective for managing neurogenic ED in rats with bilateral cavernous nerve injury (BCNI). Methods We used eight-week-old male Wistar-ST rats. The rats were divided into four groups: Sham+SiR650 (control compound) (n=5), Sham+NORD-1 (n=5), BCNI+SiR650 (n=6), and BCNI+NORD-1 (n=6). Initially, sham or BCNI surgery was performed under anesthesia in each group. BCNI surgery was performed by crushing the bilateral cavernous nerves. Four weeks post-surgery, erectile function before and after the injection of each compound into the penile corpus cavernosum was evaluated based on the change in intracavernous pressure (ICP) under electrical stimulation of the cavernous nerve. The changes in ICP with and without light irradiation were also evaluated after the administration of each compound. Results Before administering each treatment without light irradiation, the ICP/mean arterial pressure (MAP) ratio under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups were lower than those in the Sham+SiR650 (P<0.01) and Sham+NORD-1 (P=0.06) groups. After the each treatment without light irradiation, the ICP/MAP ratio under stimulation in the Sham+NORD-1 group was slightly higher than that in the Sham+SiR650 group. However, the ICP/MAP ratio under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups remained significantly lower (P<0.05 and P<0.01, respectively). After the treatment with light irradiation, the ICP/MAP ratios under stimulation in the Sham+NORD-1 and BCNI+NORD-1 groups were significantly higher than those in the Sham+SiR650 (P<0.01) and BCNI+NORD-1 (P<0.01) groups, respectively. Conclusions The combination of NORD-1 and light irradiation may be useful for treating neurogenic ED, although its toxicity must be evaluated. Disclosure Work supported by industry: no.