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.
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