Prevention of Vasculogenic Erectile Dysfunction in Rat Model by the Chronic Administration of Oral Rho Kinase Inhibitor

Purpose: Since Rho-Rho kinase calcium sensitizing pathway is being regarded as a potential target not only for the treatment of erectile dysfunction but also atherosclerosis, we designed a study to prevent vasculogenic erectile dysfunction in an atherosclerotic rat model by chronic administration of fasudil, oral Rho kinase inhibitor. Materials and Methods: Rats (3 months old) were divided into 3 groups (n=10 in each group): control (group 1), atherosclerosis (group 2), and fasudiltreated (group 3). The group 2, 3 received atherosclerosis-prone treatment but group 3 was concurrently treated by fasudil (30mg/kg/day) for 6 weeks. Following the treatment, the erectile function and the amount of pelvic atherosclerosis amount were determined. Cavernosal tissues were prepared for Western blot and malondialdehyde (MDA) assay. Results: Compared to group 2, the progression of atherosclerosis in iliac and pudendal arteries was significantly suppressed by the chronic administration of fasudil. Also the treatment lowered the level of malondialdehyde in the cavernosal tissue. The results of Western blot revealed that systemically administered fasudil could ameliorate cavernosal molecular environment characterized by the decreased expression of Rho A, transforming growth factor-beta 1 and overexpression of endothelial nitric oxide synthase. As a result, erectile function was maintained by the treatment. Conclusions: These results indicate that Rho/Rho kinase pathway is substantially involved in the development of penile erection and pelvic atherosclerosis, both of which could be prevented by chronic treatment of fasudil. Thus, Rho-kinase might be considered as a novel target for prevention of vasculogenic erectile dysfunction. (Korean J Urol 2006;47:322-330) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ