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Clinical and Developmental Immunology
Volume 2013, Article ID 263846, 11 pages
Research Article

Treatment with CB2 Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

1Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Station 17, BM 5115, CH-1015 Lausanne, Switzerland
2Division of Cardiology, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64, Avenue de la Roseraie, 1211 Geneva, Switzerland
3First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, 6 viale Benedetto XV, 16132 Genoa, Italy
4Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901 Belo Horizonte, MG, Brazil

Received 23 July 2013; Revised 8 September 2013; Accepted 9 September 2013

Academic Editor: Federico Carbone

Copyright © 2013 Rodrigo Araujo Fraga-Silva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hypercholesterolemia is one of the most important risk factors for erectile dysfunction, mostly due to the impairment of oxidative stress and endothelial function in the penis. The cannabinoid system might regulate peripheral mechanisms of sexual function; however, its role is still poorly understood. We investigated the effects of CB2 activation on oxidative stress and fibrosis within the corpus cavernosum of hypercholesterolemic mice. Apolipoprotein-E-knockout mice were fed with a western-type diet for 11 weeks and treated with JWH-133 (selective CB2 agonist) or vehicle during the last 3 weeks. CB2 receptor expression, total collagen content, and reactive oxygen species (ROS) production within the penis were assessed. In vitro corpus cavernosum strips preparation was performed to evaluate the nitric oxide (NO) bioavailability. CB2 protein expression was shown in cavernosal endothelial and smooth muscle cells of wild type and hypercholesterolemic mice. Treatment with JWH-133 reduced ROS production and NADPH-oxidase expression in hypercholesterolemic mice penis. Furthermore, JWH-133 increased endothelial NO synthase expression in the corpus cavernosum and augmented NO bioavailability. The decrease in oxidative stress levels was accompanied with a reduction in corpus cavernosum collagen content. In summary, CB2 activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice.