The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower oesophageal sphincter.
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.
De Man
J G
JG
Division of Gastroenterology, Faculty of Medicine, University of Antwerp UIA, Belgium.
Pelckmans
P A
PA
Boeckxstaens
G E
GE
Bult
H
H
Oosterbosch
L
L
Herman
A G
AG
Van Maercke
Y M
YM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000294:innervation / Q000502:physiology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D006454:Hemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001120:Arginine