Oral L-citrulline supplementation improves erectile function and penile structure in castrated rats

Objectives: 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+l-citrulline). 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-arginine-to-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.