Treatment with CB2Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

Author:

Fraga-Silva Rodrigo Araujo1,Costa-Fraga Fabiana Pereira1,Montecucco Fabrizio23ORCID,Faye Younouss1,Savergnini Silvia Quintao1,Lenglet Sébastien2,Mach François2,Steffens Sabine2,Stergiopulos Nikolaos1,Souza dos Santos Robson Augusto4,da Silva Rafaela Fernandes4

Affiliation:

1. Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Station 17, BM 5115, CH-1015 Lausanne, Switzerland

2. Division of Cardiology, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64, Avenue de la Roseraie, 1211 Geneva, Switzerland

3. First 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

4. Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901 Belo Horizonte, MG, Brazil

Abstract

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 CB2activation 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 CB2agonist) or vehicle during the last 3 weeks. CB2receptor expression, total collagen content, and reactive oxygen species (ROS) production within the penis were assessed.In vitrocorpus cavernosum strips preparation was performed to evaluate the nitric oxide (NO) bioavailability. CB2protein 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, CB2activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Publisher

Hindawi Limited

Subject

General Medicine,Immunology,Immunology and Allergy

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