Introduction Oral l-citrulline supplementation increases serum l-arginine levels more efficiently than l-arginine itself and increases nitric oxide (NO) production. Aim 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. Main Outcome Measures 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.

Abbreviations & AcronymsObjectives: To investigate the efficacy of oral L-citrulline for erectile dysfunction and penile structure disruption in a rat model. Methods: Male Wistar-ST rats aged 15 weeks were randomly divided into three groups as follows: sham-operated rats (control group), surgically castrated rats (castrated group) and surgically castrated rats subsequently treated with 2% L-citrulline water (castrated + Lcitrulline). At 4 weeks postoperative, erectile function was assessed based on intracavernous pressure changes, followed by electrostimulation of cavernous nerves and calculation of maximum intracavernous pressure/mean arterial pressure. Penile structure was evaluated by Masson's trichrome staining and the smooth muscle-to-collagen ratio was calculated. The serum bioavailable testosterone, L-arginine, L-citrulline, N G ,N G -dimethylarginine and nitrogen oxide levels were evaluated. Results: The bioavailable testosterone concentrations were decreased in the castrated and castrated + L-citrulline groups compared with the control group at 4 weeks after surgery. The intracavernous pressure-to-mean arterial pressure and smooth muscle-to-collagen ratios were significantly decreased in the castrated group compared with the control group, but significantly increased in the castrated + L-citrulline group compared with the castrated group. The serum L-citrulline, L-arginine and N G ,N G -dimethylarginine levels, and the L-arginineto-N G ,N G -dimethylarginine ratios were significantly increased in the castrated + L-citrulline group compared with the castrated group. The serum nitrogen oxide levels were increased in the castrated + L-citrulline group compared with the castrated group. Conclusions: Oral L-citrulline can improve the erectile response to electric stimulation of cavernous nerve and penile structure in castrated rats.