Efficacy of a Red-Light Controllable Nitric Oxide Releaser for Neurogenic Erectile Dysfunction: A Study Using a Rat Model of Cavernous Nerve Injury.

Abstract

Neurogenic erectile dysfunction (ED) is a common side effect of radical prostatectomy (RP) because of cavernous nerve damage. In these patients, the production of nitric oxide (NO), which is important for erection, is decreased in the corpus cavernosum. Therefore, NO donors are useful for post-RP ED. However, short half-life and systemic side effects are problems of NO application in ED therapy. To avert these problems, we developed a red-light controllable NO releaser, NORD-1. This study aimed to investigate the effect of NORD-1 and red-light irradiation on neurogenic ED using a rat model of bilateral cavernous nerve injury (BCNI). BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope. Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p<0.05). After injecting NORD-1 into the penis, erectile function did not change without red-light irradiation. However, the combination of NORD-1 and red-light irradiation significantly improved erectile function (p<0.05) without affecting systemic arterial pressure. In contrast, when SiR650 was used, erectile function did not change in all three conditions. NORD-1 was detected only in the corpus cavernosum and not in the urethra and dorsal vein. NORD-1 combined with red-light irradiation is effective for ED induced by cavernous nerve injury. This treatment may have low risks of hypotension and urinary incontinence, and it can replace the current treatment for post-RP ED.