l-Arginine-induced relaxation of the internal anal sphincter is not mediated by nitric oxide

Abstract

Abstract Background Topical application of l-arginine, the precursor of nitric oxide, reduces resting anal pressure without significant side-effects and may therefore be of benefit in the treatment of anal fissure. This in vitro study investigated the effect of l-arginine on sheep and human isolated internal anal sphincter (IAS) to ascertain the role played by nitric oxide and guanosine 3′,5′-cyclic monophosphate. Methods Strips of sheep and human IAS were mounted in isolated organ baths. The effects on myogenic tone of increasing concentrations of l-arginine, d-arginine and other amino acids were evaluated. Results l-Arginine, d-arginine and other basic amino acids (l-lysine and l-ornithine) all caused a concentration-dependent reduction in myogenic tone. l-Arginine was the most effective and produced a mean(s.e.m.) maximal reduction in myogenic tone of 78·2(7·1) and 40·2(9·3) per cent in sheep and human tissue respectively. These responses were not affected by NG-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase. Changes in pH per se were unable to explain the relaxation fully, but an equiosmolar sodium chloride solution produced a concentration–response relationship similar to that of l-arginine. Conclusion The ability of l-arginine to reduce myogenic tone is independent of nitric oxide. This effect may be partially pH dependent but the osmolality of the solution appears to be a major factor. Hyperosmolar solutions might be worthy of further investigation as agents that affect anal tone.