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Treatment with CB(2) Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

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 understoo...

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Detalles Bibliográficos
Autores principales: Fraga-Silva, Rodrigo Araujo, Costa-Fraga, Fabiana Pereira, Montecucco, Fabrizio, Faye, Younouss, Savergnini, Silvia Quintao, Lenglet, Sébastien, Mach, François, Steffens, Sabine, Stergiopulos, Nikolaos, Souza dos Santos, Robson Augusto, da Silva, Rafaela Fernandes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835849/
https://www.ncbi.nlm.nih.gov/pubmed/24302957
http://dx.doi.org/10.1155/2013/263846
Descripción
Sumario: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 CB(2) 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 CB(2) agonist) or vehicle during the last 3 weeks. CB(2) 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. CB(2) 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, CB(2) activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice.