The role of nitric oxide in inhibitory non‐adrenergic non‐cholinergic neurotransmission in the canine lower oesophageal sphincter

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Abstract
1 The role of nitric oxide (NO) in non-adrenergic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the canine lower oesophageal sphincter (LOS). Electrical field stimulation evoked frequency-dependent relaxations, which were resistant to adrenergic and cholinergic blockade and abolished by tetrodotoxin. 2 Exogenous administration of NO induced concentration-dependent and tetrodotoxin-resistant relaxations which mimicked those in response to electrical stimulation. 3 NG-nitro-l-arginine (l-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stimulation but not those by exogenous NO or vasoactive intestinal polypeptide (VIP). 4 The effect of l-NNA was prevented by l-arginine, the precursor of the NO biosynthesis but not by its enantiomer d-arginine. 5 Haemoglobin abolished the NO-induced responses and reduced those evoked by electrical stimulation. 6 Cumulative administration of VIP induced concentration-dependent relaxations, which were slow in onset and sustained. A complete relaxation to VIP was not achieved and the relaxations were not affected by l-NNA. 7 In conclusion, our results provide evidence that NANC relaxations are mediated by NO, suggesting NO or a NO releasing substance as the final inhibitory NANC neurotransmitter in the canine LOS.