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, W. J G Hellstrom

Research output: Contribution to journalArticle

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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 (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
Volume52
Issue number2
DOIs
StatePublished - Aug 1 2007

Fingerprint

Erectile Dysfunction
Cocaine
Nitric Oxide Synthase Type III
Endothelin-1
Peroxidase
Nitric Oxide
Endothelin B Receptors
Endothelin A Receptors
Pressure
Control Groups
Injections
Penis
Nitrites
Baths
Nitrates
Endothelium
Sprague Dawley Rats
Reactive Oxygen Species
Students

Keywords

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

ASJC Scopus subject areas

  • Urology

Cite this

Kendirci, M., Pradhan, L., Trost, L., Gur, S., Chandra, S., Agrawal, K. C., & Hellstrom, W. J. G. (2007). Peripheral Mechanisms of Erectile Dysfunction in a Rat Model of Chronic Cocaine Use. European Urology, 52(2), 555-564. https://doi.org/10.1016/j.eururo.2007.03.022

Peripheral Mechanisms of Erectile Dysfunction in a Rat Model of Chronic Cocaine Use. / Kendirci, Muammer; Pradhan, Leena; Trost, Landon; Gur, Serap; Chandra, Surabhi; Agrawal, Krishna C.; Hellstrom, W. J G.

In: European Urology, Vol. 52, No. 2, 01.08.2007, p. 555-564.

Research output: Contribution to journalArticle

Kendirci, M, Pradhan, L, Trost, L, Gur, S, Chandra, S, Agrawal, KC & Hellstrom, WJG 2007, 'Peripheral Mechanisms of Erectile Dysfunction in a Rat Model of Chronic Cocaine Use', European Urology, vol. 52, no. 2, pp. 555-564. https://doi.org/10.1016/j.eururo.2007.03.022
Kendirci, Muammer ; Pradhan, Leena ; Trost, Landon ; Gur, Serap ; Chandra, Surabhi ; Agrawal, Krishna C. ; Hellstrom, W. J G. / Peripheral Mechanisms of Erectile Dysfunction in a Rat Model of Chronic Cocaine Use. In: European Urology. 2007 ; Vol. 52, No. 2. pp. 555-564.
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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 (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.",
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AB - 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.

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