title: Oral L-citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction.
abstract: BACKGROUND
  Oral L-citrulline supplementation increases serum L-arginine levels more efficiently than L-arginine itself and increases nitric oxide (NO) production.
  
  
  OBJECTIVE
  To investigate whether oral L-citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction (ED).
  
  
  METHODS
  We divided 8-week-old male Wistar-ST rats into 3 groups: sham-operated rats (control group), arteriogenic ED rats who underwent ligation of both internal iliac arteries (ligation group), and arteriogenic ED rats receiving oral 2% L-citrulline water supplementation (citrulline group). Citrulline water was given to arteriogenic ED rats for 3 weeks from 1 week after surgery. Erectile function was evaluated by maximum intracavernous pressure/mean arterial pressure (ICP/MAP) ratios via cavernous nerve stimulation at 4 weeks after surgery. Then, the penises were resected, stained with Masson's trichrome, and observed microscopically. Serum nitrogen oxides (NOx) levels were measured by high-performance liquid chromatography. Bonferroni's multiple t-test was used for statistical analysis.
  
  
  METHODS
  The main outcome measures were changes in ICP/MAP, smooth muscle (SM)/collagen ratios, and NOx levels following L-citrulline supplementation.
  
  
  RESULTS
  The ICP/MAP ratio in the ligation group was significantly lower than that in the control group (P<0.05), denoting ED. The ICP/MAP ratio of the citrulline group was significantly higher than that of the ligation group (P<0.05), indicating ED amelioration. Levels of NOx in the ligation group were significantly lower than in the control group (P<0.05), while those in the citrulline group were significantly higher than in the ligation group (P<0.05). SM/collagen ratios in the ligation group were significantly lower than in the control group (P<0.05), while ratios in the citrulline group were significantly higher than those in the ligation group (P<0.05).
  
  
  CONCLUSIONS
  Oral L-citrulline supplementation improved ICP/MAP and SM/collagen ratios and increased NOx. Therefore, oral L-citrulline supplementation might be a useful novel therapy for acute arteriogenic ED.
authors.affiliation: Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Arufumi
authors.initials: A
authors.lastname: Shiota
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hotta
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kataoka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000008:administration & dosage*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018783:Impotence, Vasculogenic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000097:blood; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002956:Citrulline; D009569:Nitric Oxide; D003094:Collagen
keywords: Arteriogenic; Erectile Dysfunction; Improvement of Erectile Function; Nitric Oxide; l-Citrulline