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Abstract

Volume 8, Issue 2 (March 2006) 8, 159–167; 10.1111/j.1745-7262.2006.00122.x

Evaluation of tetrahydrobiopterin (BH4) as a potential therapeutic agent to treat erectile dysfunction

Frank Sommer, Theodor Klotz, Dirk Steinritz and Wilhelm Bloch

1.Department of Mens Health, Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, DE-20264, Germany
2.Department of Urology, Medical Clinic Weiden, Weiden DE-9263 7, Germany
3.Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne DE-50927, Germany

Correspondence: Prof. Frank Sommer, Department of Mens Health, Department of Urology, University Medical Center Hamburg-Eppendorf, Postfach 202101, Hamburg, DE-20264, Germany. Fax: +49-40-42803-4734. E-mail: Frank.Sommer@men-and-health.info

Received 24 May 2005; Accepted 29 November 2005

Abstract

Aim: Nitric oxide (NO)-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase (eNOS) coenzyme tetrahydrobiopterin (BH4) converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation.

Methods: Using quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction (ED) while receiving visual sexual stimulation.

Results: 8-isoprostane content in endothelium and smooth muscle was significantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of > 60% penile rigidity (33.5 min [95% confidence interval (CI): 13.1–49.3] at base and 29.4 min [95% CI: 8.9–42.2] at tip). A 500-mg dose increased the relative duration of > 60% penile rigidity by 36.1 min (95% CI: 16.3–51.8) at the base and 33.7 min (95% CI: 11.4–43.9) at the tip. Treatments were well tolerated.

Conclusion: BH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS.

Keywords: tetrahydrobiopterin, nitric oxide, 8-isoprostane, nitrotyrosine, erectile dysfunction

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.