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.
Highlights
Erectile dysfunction (ED) is a common type of sexual dysfunction, which is characterized by an inability to achieve and maintain an erection for sexual performance
We investigated the toxic effects of ketamine in reproduction system with focus on erectile tissues
We showed that long-term ketamine administration deteriorated erectile function
Summary
Erectile dysfunction (ED) is a common type of sexual dysfunction, which is characterized by an inability to achieve and maintain an erection for sexual performance. It is associated with aging and many common systemic disorders such as diabetes mellitus and hypertension [1, 2]. Recent studies have stated that repeated application of ketamine in rats affects production of nitric oxide synthase (NOS) and induces apoptosis in the urothelial cell [10, 11]. Some studies have demonstrated that ketamine induces cytotoxicity in neurons through induction of apoptosis and changes of neuronal nitric oxide synthase (nNOS) expression [14, 15]
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