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The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction

International Journal of Impotence Research volume 17, pages 409–416 (2005)Cite this article

Abstract

This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia. First of all, in order to investigate whether chronic administration of DA-8159 prevents the development of erectile dysfunction associated with hypercholesterolemia, male SD rats were divided into four groups (normal control, hypercholesterolemic control, DA-8159 5 or 20 mg/kg/day). Over a 5-month period, the animals were fed a 2% cholesterol diet and administered DA-8159 orally once a day. After 5 months, the electrostimulation-induced penile erection and the vascular function using acetylcholine-induced vasodilation with endothelium-intact aortic rings were examined. Furthermore, the plasma lipid profiles, endothelin and NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA) concentrations were measured. In order to investigate the acute treatment effect of DA-8159 on the erectile function in an established hypercholesterolemic model, additional animals were given a 2% cholesterol diet for 5 months without DA-8159. At the end of 5 months, the rats were divided into three groups (hypercholesterolemic control, DA-8159 0.3 or 1 mg/kg). DA-8159 was administered intravenously 1 min prior to the intracavernous pressure (ICP) measurement. In a chronic treatment study, while the hypercholesterolemic control showed a significantly lower erectile function, vascular reactivity, and increased plasma cholesterol, endothelin and ADMA concentration, the chronic DA-8159 treatment clearly restored the erectile responses by electric stimulation, preserved the potential of thoracic aortic relaxation in a dose-dependent manner, and significantly decreased the plasma endothelin and ADMA concentrations. In an acute treatment study, DA-8159 induced a dose- and frequency-dependent increase in ICP. The ICP/BP ratio and the corresponding AUC values, and the detumescence time were also significantly increased compared to the hypercholesterolemic control. These results suggest that DA-8159 is beneficial for erectile dysfunction in a rat hypercholesterolemic model and provided a rationale for the potential use of DA-8159 for treating erectile dysfunction secondary to hypercholesterolemia.

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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. Preclinical Division, Research Laboratories of Dong-A Pharmaceutical Company, Sangal, Kiheung, Youngin, Kyunggi, Republic of Korea

    K K Kang, J Y Yu, M Yoo & J W Kwon

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  1. K K Kang
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  2. J Y Yu
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  3. M Yoo
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  4. J W Kwon
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Correspondence to K K Kang.

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Kang, K., Yu, J., Yoo, M. et al. The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction. Int J Impot Res 17, 409–416 (2005). https://doi.org/10.1038/sj.ijir.3901331

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