L-arginine-induced relaxation of the internal anal sphincter is not mediated by nitric oxide.
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 N(G)-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.


CONCLUSIONS
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.
Acheson
A G
AG
Department of Surgery, Centre for Integrative Systems Biology and Medicine, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. austin.acheson@nottingham.ac.uk
Griffin
N
N
Scholefield
J H
JH
Wilson
V G
VG
D001003:Anal Canal / Q000187:drug effects*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012756:Sheep
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester