Peripheral Mechanisms of Erectile Dysfunction in a Rat Model of Chronic Cocaine Use

Muammer Kendirci, Leena Pradhan, Landon Trost, Serap Gur, Surabhi Chandra, Krishna C. Agrawal, Wayne J.G. Hellstrom

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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 (ETAR and ETBR), 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 ETAR expression compared with saline controls, while ETBR 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. Conclusion: 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 ETAR expression, increased penile MPO activity, and reduced penile eNOS expression.

Original languageEnglish (US)
Pages (from-to)555-564
Number of pages10
JournalEuropean Urology
Issue number2
StatePublished - Aug 2007
Externally publishedYes


  • Cocaine
  • Corpus cavernosum
  • Endothelial dysfunction
  • Endothelin
  • Endothelium
  • Erectile dysfunction
  • Myeloperoxidase
  • Nitric oxide
  • Reactive oxygen species

ASJC Scopus subject areas

  • Urology


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