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A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats

International Journal of Impotence Research volume 16, pages 479–485 (2004)Cite this article

Abstract

We compared the effects of a nitric oxide (NO)-releasing sildenafil (NCX-911), NO-independent soluble guanylate cyclase activator (BAY41-2272) and sildenafil on the anococcygeus muscle from streptozotocin-induced 16-weeks diabetic rats. NCX-911, BAY41-2272 and sildenafil reduced the phenylephrine-induced tone in the control group (EC50=1088.8±165.0, 151.6±9.3 and 827.1±167.3 nM, respectively). The potencies of NCX-911 and BAY41-2272 were not altered, but that of sildenafil was significantly reduced in the diabetic group. EC50 values for NCX-911, BAY41-2272 and sildenafil in the diabetic group were 1765.9±303.5, 209.7±27.3 and 2842.2±640.3 nM, respectively (P<0.05 for sildenafil). Nitrergic relaxation responses were significantly decreased in the diabetic group. The remaining nitrergic relaxation responses were potentiated by BAY41-2272 but not by sildenafil or NCX-911. These results confirm that endogenous NO derived from nitrergic nerves is significantly decreased in diabetes, and suggest that NO-releasing PDE5 inhibitors and NO-independent soluble guanylate cyclase activators could be more useful than PDE5 inhibitors in the treatment of ED in long-term diabetes.

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Acknowledgements

This work was supported by St Peter's Andrology Research Fund and Juvenile Diabetes Research Foundation. JS Kalsi is a recipient of the Young Investigator's Award from the International Society for Sexual and Impotence Research. S Cellek is a fellow of Juvenile Diabetes Research Foundation. The authors thank NicOx (France) and Bayer (Germany) for providing the compounds.

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Authors and Affiliations

  1. Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London, UK

    Jasjit S Kalsi, David J Madge & Selim Cellek

  2. The St Peter's Andrology Centre, University College London, London, UK

    Jasjit S Kalsi, David J Ralph & Phil D Kell

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  1. Jasjit S Kalsi
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Correspondence to Selim Cellek.

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Kalsi, J., Ralph, D., Madge, D. et al. A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats. Int J Impot Res 16, 479–485 (2004). https://doi.org/10.1038/sj.ijir.3901224

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