title: Treatment with CB2 agonist JWH-133 reduces histological features associated with erectile dysfunction in hypercholesterolemic mice.
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 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.
authors.affiliation: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Station 17, BM 5115, CH-1015 Lausanne, Switzerland.
authors.forename: Rodrigo Araujo
authors.initials: RA
authors.lastname: Fraga-Silva
authors.forename: Fabiana Pereira
authors.initials: FP
authors.lastname: Costa-Fraga
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.forename: Younouss
authors.initials: Y
authors.lastname: Faye
authors.forename: Silvia Quintao
authors.initials: SQ
authors.lastname: Savergnini
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Sabine
authors.initials: S
authors.lastname: Steffens
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Stergiopulos
authors.forename: Robson Augusto Souza
authors.initials: RA
authors.lastname: dos Santos
authors.forename: Rafaela Fernandes
authors.initials: RF
authors.lastname: da Silva
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D005355:Fibrosis; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D008055:Lipids; D017382:Reactive Oxygen Species; D043885:Receptor, Cannabinoid, CB2; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC