Melatonin Improves Erectile Function in Rats With Chronic Lower Body Ischemia

J Sex Med. 2016 Feb;13(2):179-86. doi: 10.1016/j.jsxm.2015.12.018. Epub 2016 Jan 20.


Introduction: Arterial occlusive disease is the leading cause of erectile dysfunction (ED). Using an established rat model we wanted to characterize the changes caused by atherosclerosis-induced chronic ischemia on penile structures and erectile function.

Aim: To investigate the effect of melatonin on these parameters.

Methods: Adult male Sprague-Dawley rats were divided into control, arterial injury (AI) and AI with melatonin treatment groups. AI and AI-melatonin groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI surgery for 8 weeks. AI-melatonin group rats received melatonin (20 mg/kg/day) orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, erectile function was tested. Corpus cavernosum (CC) tissues were processed for pharmacological and immunohistochemical studies, histological examination, and Western blotting.

Main outcome measures: Apomorphine test was performed to evaluate erectile function. Organ bath study was performed to measure the CC-contraction induced by KCl and phenylephrine, and relaxation induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP).

Results: The number of erectile responses was significantly lower in the AI group (2.5 ± 0.5/hour) than in the control (5.0 ± 0.7/hour) and in the melatonin-treated groups (5.0 ± 0.3/hour). The responses to phenylephrine were lower in the AI-groups than in the controls, but there were no differences between control and AI-melatonin groups. SNP-induced relaxation in the AI-melatonin group was higher than in the AI, but lower than in control group. The EFS-elicited relaxation responses in the AI group were significantly lower than in the control and AI-melatonin groups. Compared to controls, CC tissues from the AI group showed significantly higher collagen content, and lower protein expression of eNOS and nNOS, and increased expression of iNOS. These changes were reduced or prevented by melatonin treatment.

Conclusion: Treatment with melatonin reduced/prevented functional and morphological changes induced by chronic ischemia on penile structure and function.

Keywords: Arterial Occlusive Disease; Chronic Penile Ischemia; Erectile Dysfunction; High-Cholesterol Diet; Melatonin; Oxidative Stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Atherosclerosis / complications*
  • Cholesterol, Dietary
  • Chronic Disease
  • Disease Models, Animal
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / physiopathology
  • Humans
  • Ischemia / complications*
  • Ischemia / physiopathology
  • Male
  • Melatonin / pharmacology*
  • Penile Erection / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Antioxidants
  • Cholesterol, Dietary
  • Melatonin