title: Melatonin Improves Erectile Function in Rats With Chronic Lower Body Ischemia.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Treatment with melatonin reduced/prevented functional and morphological changes induced by chronic ischemia on penile structure and function.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo city, Yamanashi, Japan. Electronic address: nsawada@yamanashi.ac.jp.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama, Fukushima, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Zarifpour
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo city, Yamanashi, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo city, Yamanashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000150:complications*; D002791:Cholesterol, Dietary; D002908:Chronic Disease; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D002791:Cholesterol, Dietary; D008550:Melatonin
keywords: Arterial Occlusive Disease; Chronic Penile Ischemia; Erectile Dysfunction; High-Cholesterol Diet; Melatonin; Oxidative Stress