백서에서 경구용 Rho Kinase 억제제인 Fasudil의 만성 투여에 의한 혈관성 발기부전의 예방효과
Prevention of Vasculogenic Erectile Dysfunction in Rat Model by the Chronic Administration of Oral Rho Kinase Inhibitor
박관진, 박민영, 김수웅, 백재승,
소속 상세정보
박관진 ( Park Kwan-Jin )
원자력병원 비뇨기과
박민영 ( Park Min-Young )
서울대학교 의과대학 비뇨기과학교실
김수웅 ( Kim Soo-Woong )
서울대학교 의과대학 비뇨기과학교실
백재승 ( Paick Jae-Seung )
서울대학교 의과대학 비뇨기과학교실
KMID : 0358320060470030322
Abstract
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 fasudil- treated(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.
Conclusion: 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)
키워드
Vasculogenic Impotence;Atherosclerosis;Rats;Rho GTP binding proteins
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