title: An increased arginase activity is associated with corpus cavernosum impairment induced by hypercholesterolemia.
abstract: BACKGROUND
  Hypercholesterolemia is a prevalent risk factor for the development of erectile dysfunction (ED), mostly due to an increase in oxidative stress and impaired nitric oxide (NO) bioavailability within the penis. Arginase is an enzyme that shares the common substrate L-arginine with NO synthase. Augmented arginase activity reduces NO production and is associated with ED development. However, the contribution of arginase hyperactivity in hypercholesterolemia-induced ED is unknown.
  
  
  OBJECTIVE
  In the present study, we investigated the activity and role of arginase in the corpus cavernosum of hypercholesterolemic mice.
  
  
  METHODS
  Apolipoprotein E (ApoE) gene-deleted mice fed with a Western-type diet for 11 weeks were treated with the selective arginase inhibitor, N-ω-Hydroxy-L-norarginine (NOHA), or vehicle (saline 0.9%) during the last 9 weeks. Arginase activity and expression were measured in penis protein extraction. Reactive oxygen species (ROS) content within the corpus cavernosum was measured by dihydroethidium staining. Functional in vitro studies were performed using cavernosal strips mounted in an isometric organ bath to evaluate NO production.
  
  
  METHODS
  Arginase activity and its role in modulating NO and ROS production within the corpus cavernosum of hypercholesterolemic mice is the main outcome measure.
  
  
  RESULTS
  Total arginase activity and arginase type II protein expression were increased in hypercholesterolemic mice compared with wild-type mice. The long-term treatment with NOHA normalized this alteration. Moreover, pharmacological arginase inhibition by NOHA attenuated the augmented ROS production within the corpus cavernosum of ApoE(-/-) mice, which increased the NO-dependent response in cavernosal strips.
  
  
  CONCLUSIONS
  These evidences indicate that arginase hyperactivity is associated with ED induced by hypercholesterolemia, suggesting that this enzyme is a potential target for treating ED.
authors.affiliation: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Fraga-Silva
authors.forename: Fabiana P
authors.initials: FP
authors.lastname: Costa-Fraga
authors.forename: Younoss
authors.initials: Y
authors.lastname: Faye
authors.forename: Mikaël
authors.initials: M
authors.lastname: Sturny
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.forename: Rafaela F
authors.initials: RF
authors.lastname: da Silva
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Stergiopulos
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000201:enzymology* / Q000209:etiology; D006937:Hypercholesterolemia / Q000150:complications / Q000201:enzymology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010413:Penis / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C021064:norarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase
keywords: Arginase; Erectile Dysfunction; Hypercholesterolemia; L-arginine; Nitric Oxide; Oxidative Stress