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

Research output: Contribution to journalArticle

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
JournalOncotarget
DOIs
Publication statusE-pub ahead of print - Jul 20 2016

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Nitric Oxide Synthase Type I
Ketamine
Erectile Dysfunction
Smooth Muscle Myocytes
Apoptosis
Nitric Oxide Synthase Type II
Smooth Muscle
Nitric Oxide Synthase Type III
Intraperitoneal Injections
Pressure
In Situ Nick-End Labeling
Sprague Dawley Rats
Control Groups

Keywords

  • Journal Article

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

In: Oncotarget, 20.07.2016.

Research output: Contribution to journalArticle

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AU - Liao, Chun-Hou

AU - Chiueh, Tzong-Shi

AU - Lin, Yuh-Feng

AU - Chiang, Han-Sun

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N2 - 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.

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