title: Peripheral mechanisms of erectile dysfunction in a rat model of chronic cocaine use.
abstract: OBJECTIVE
  To evaluate the peripheral mechanisms of erectile dysfunction (ED) in a rat model of triple-binge cocaine administration.
  
  
  METHODS
  Adult male Sprague-Dawley rats (n=24) were divided into two groups: group 1, control rats receiving vehicle (saline); group 2, rats receiving binge cocaine injections. After completion of triple-binge cocaine or saline injections, both groups underwent an in vivo, neurogenic-mediated erectile response protocol to assess intracavernosal pressure (ICP). Penile endothelin-A and -B receptors (ET(A)R and ET(B)R), plasma levels of big endothelin-1 (big-ET-1), and endothelial nitric oxide synthase (eNOS) protein expression were assessed. To analyze nitric oxide (NO) production, we measured plasma nitrate-nitrite levels and quantitated myeloperoxidase (MPO) activity in cavernosal tissues to determine reactive oxygen species generation. Endothelium-dependent and -independent relaxation responses were evaluated in vitro. Data were analyzed with Student t test.
  
  
  RESULTS
  Triple-binge cocaine administration caused significantly decreased erectile responses as measured by ICP in vivo. Plasma big-ET-1 levels were significantly increased in the triple-binge cocaine treatment group compared with control animals. In the penis, triple-binge cocaine administration significantly increased ET(A)R expression compared with saline controls, while ET(B)R expression was not altered. Cocaine-treated rats had significantly decreased eNOS expression and NO production. The activity of tissue MPO was significantly increased in the cocaine group compared with control rats. Organ bath studies demonstrated that triple-binge cocaine resulted in a 64% reduction in maximal relaxation compared with the control group.
  
  
  CONCLUSIONS
  This study demonstrates that triple-binge cocaine administration significantly reduces erectile function in rats. The pathophysiologic mechanisms that are likely involved include increased plasma big-ET-1 levels, increased penile ET(A)R expression, increased penile MPO activity, and reduced penile eNOS expression.
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Muammer
authors.initials: M
authors.lastname: Kendirci
authors.forename: Leena
authors.initials: L
authors.lastname: Pradhan
authors.forename: Landon
authors.initials: L
authors.lastname: Trost
authors.forename: Serap
authors.initials: S
authors.lastname: Gur
authors.forename: Surabhi
authors.initials: S
authors.lastname: Chandra
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Agrawal
authors.forename: Wayne J G
authors.initials: WJ
authors.lastname: Hellstrom
mesh_terms: D000818:Animals; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D007172:Erectile Dysfunction / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016232:Endothelins; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase