Abstract

Exogenous nitric oxide donors, such as glyceryl trinitrate, have been used as treatment for anal fissures; however, headaches develop in 60 percent of patients. Nitric oxide produced from the cellular metabolism of L-arginine mediates relaxation of the internal anal sphincter. This study investigated whether topical L-arginine gel reduces maximum anal resting pressure in volunteers. In a two-center study, volunteers received a single topical dose of L-arginine or placebo (Aquagel ). Anal manometry was performed for two hours after application of 400 mg of L-arginine gel or placebo gel to the anal verge in 25 volunteers. Side effects were recorded after single application and also after repeated dosing for three days. L-Arginine reduced maximum anal resting pressure by 46 percent from a median of 65 cm of water to a minimal value of 35 cm of water ( P< 0.001, Wilcoxon's signed-rank test). The difference between L-arginine and placebo using repeated-measures testing was significant at P< 0.005. No side effects occurred with either gel; in particular, no episodes of headache were recorded. Topical L-arginine gel significantly lowers maximum anal resting pressure; its onset of action is rapid, and duration is at least two hours ( P< 0.01). L-arginine may have therapeutic potential, but further evaluation is needed before it can be used as a possible alternative treatment for chronic anal fissure.

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