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The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits

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Abstract

A previous study showed that DA-8159, a potent type 5 phosphodiesterase inhibitor, enhanced the relaxation of the smooth muscles in the normal rabbit corpus cavernosum. In this study, we investigated the in vitro effects of DA-8159 on cavernosal smooth muscle relaxation and the in vivo erectogenic potential in diabetic rabbits, since erectile dysfunction is a well-known sequela of diabetes mellitus. Diabetes mellitus was induced in male New Zealand White rabbits with alloxan monohydrate. Cavernosal strips from age-matched control and 8-week diabetic animals were mounted in organ baths. The relaxation responses to sodium nitroprusside (10-9∼10-5 M), a nitric oxide donor, were assessed in the presence or absence of DA-8159 (10-9∼10-6 M). For the penile erection test, DA-8159 was given orally (1~10 mg/kg) to diabetic rabbits and the length of the uncovered penile shaft was measured in a time-course manner in the presence or absence of intravenous sodium nitroprusside. The sodium nitroprusside-stimulated relaxations were significantly impaired in the corpus cavernosum from the diabetic group (IC50=1.07×10-6 M following 8 weeks of diabetes mellitus; compared with 0.48×10-6 M for age-matched controls). DA-8159 significantly and dose-dependently enhanced the sodium nitroprusside-stimulated relaxation in the diabetic groups. In addition, DA-8159 induced a dose-dependent penile erection in diabetic rabbits, which was potentiated by intravenous sodium nitroprusside. These results suggest that DA-8159 is an effective treatment for diabetic erectile dysfunction but further evaluation of the efficacy on human needs to be performed.

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Acknowledgements

This study was supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ2-PG4-PT01-0024).

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Authors and Affiliations

  1. Research Institutes, Dong-A Pharmaceutical Company, 47-5 Sanggal, Kiheung, Youngin, 449-900, Kyunggi, Korea

    Kyung Koo Kang, Seul Min Choi, Gook Jun Ahn, Jong Won Kwon & Won Bae Kim

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  1. Kyung Koo Kang
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  2. Seul Min Choi
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  3. Gook Jun Ahn
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  4. Jong Won Kwon
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  5. Won Bae Kim
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Correspondence to Kyung Koo Kang.

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Kang, K.K., Choi, S.M., Ahn, G.J. et al. The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits. Urol Res 32, 107–111 (2004). https://doi.org/10.1007/s00240-003-0387-1

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  • DOI: https://doi.org/10.1007/s00240-003-0387-1

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