Long-term administration of ketamine induces erectile dysfunction by decreasing neuronal nitric oxide synthase on cavernous nerve and increasing corporal smooth muscle cell apoptosis in rats

Hung Sheng Shang, Yi No Wu, Chun Hou Liao, Tzong Shi Chiueh, Yuh Feng Lin, Han Sun Chiang

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Abstract

We investigated and evaluated the mechanisms of erectile dysfunction (ED) in a rat model of long-term ketamine administration. Adult male Sprague-Dawley rats (n = 32) were divided into four groups: namely the control group receiving intraperitoneal injection of saline, 1-month, 2-month and 3-month groups receiving daily intraperitoneal injection of ketamine (100 mg/kg/ day) for 1, 2, and 3 month respectively. After treatment, animals underwent an erectile response protocol to assess intracavernosal pressure (ICP). Smooth muscle content was evaluated. Neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression were assessed using immunostaining assay. Ketamine-induced apoptosis was analyzed using TUNEL assay. Long-term ketamine administration caused significantly decreased erectile responses as measured by ICP. Smooth muscle content was significantly decreased in the ketamine-treated rats for 3 months. In the erectile tissue, ketamine administration significantly reduced nNOS expression and increased iNOS content compared with controls, whereas eNOS expression was not altered. Ketamine induced apoptosis in corpus cavernosum. The present study demonstrates that long-term ketamine administration led to erectile dysfunction in rat. The molecular mechanisms of ketamine-induced ED involved the increased apoptosis and up-regulated iNOS expression incorporating with loss of corporal smooth muscle content and reduced nNOS expression in cavernous nerve.

Original languageEnglish
Pages (from-to)73670-73683
Number of pages14
JournalOncotarget
Volume8
Issue number43
Early online dateJul 20 2016
DOIs
Publication statusPublished - 2017

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Keywords

  • Apoptosis
  • Corporal smooth muscle
  • Erectile dysfunction
  • Ketamine
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Oncology

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