(610) Relaxing Response to the Light-Responsive sGC Activator, GSK-Rosa, Using Rat Corpora Cavernosum

Introduction Nitric oxide/sGC pathway is important for erection and is thought to be a good target for Erectile dysfunction (ED) therapy. We previously demonstrated that the sGC activator, GSK2181236A, enhanced erectile responses in intact rats. Based on these findings, we have developed GSK-Rosa, a light-responsive compound that releases GSK2181236A upon exposure to green light. Objective In this study, we assessed whether GSK-Rosa and green light can induce relaxation of the corpus cavernosum via isometric tension study. Methods Penile corpus cavernosum tissue was excised from 8-week-old male SD rats and carefully suspended in Magnus tubes. The nitric oxide synthase inhibitor L-NAME (10 μM) was added to all preparations. The tissue was precontracted with norepinephrine (10 μM), and after reaching a plateau, either DMSO or GSK-Rosa (10 μM) was added to the tubes. Ten minutes after administration, green light (568 nm, 46 mW/cm2) was applied for three minutes. The relaxation rate was measured every ten minutes from the end of light irradiation (0 min) to 60 minutes. Results The relaxing response gradually increased over time in corpus cavernosum of the GSK-Rosa and light-treated group, while the DMSO group showed no relaxation. Although no statistically significant difference was observed, the GSK-Rosa-treated group consistently showed greater relaxation than the DMSO group at 40, 50, and 60 minutes after green light irradiation. The relaxation rates at 40 minutes were 53% ± 31% for GSK-Rosa and 22% ± 9.2% for DMSO. At 50 minutes, the rates were 54% ± 31% for GSK-Rosa and 33% ± 7.7% for DMSO. At 60 minutes, relaxation reached 63% ± 24% for GSK-Rosa compared to 39% ± 14% for DMSO. Conclusions GSK-Rosa induces sustained relaxation of the rat corpus cavernosum in response to green light exposure, allowing precise control of the initiation of the erectile response with light. These findings suggest that GSK-Rosa might be a promising light-responsive sGC activator as a novel treatment for ED. Disclosure No