title: Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses.
abstract: The lower esophageal sphincter (LES) has a circular muscle component exhibiting spontaneous tone that is relaxed by nitric oxide (NO) and a low-tone sling muscle that contracts vigorously to cholinergic stimulation but with little or no evidence of NO responsiveness. This study dissected the responses of the sling muscle to nitrergic innervation in relationship to its cholinergic innervation and circular muscle responses. Motor responses were induced by electrical field stimulation (EFS; 1-30 Hz) of muscle strips from sling and circular regions of the feline LES in the presence of cholinergic receptor inhibition (atropine) or NO synthase inhibition [NG-nitro-L-arginine (L-NNA)+/-atropine]. This study showed the following. First, sling muscle developed less intrinsic resting tone compared with circular muscle. Second, with EFS, sling muscle contracted (most at <or=10 Hz), whereas circular muscle relaxed >50% by 5 Hz. Third, on neural blockade with atropine or L-NNA+/-atropine, 1) sling muscle, although predominantly influenced by excitatory cholinergic stimulation, had a small neural NO-mediated inhibition, with no significant non-NO-mediated inhibition and 2) circular muscle, although little affected by cholinergic influence, underwent relaxation predominantly by neural release of NO and some non-NO inhibitory influence (at higher EFS frequency). Fourth, the sling, precontracted with bethanecol, could relax with NO and some non-NO inhibition. Finally, the tension range of both muscles is similar. In conclusion, sling muscle has limited NO-mediated inhibition to potentially augment or replace sling relaxation effected by switching off its cholinergic excitation. Differences within the LES sling and circular muscles could provide new directions for therapy of LES disorders.
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada M5T 2S8.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: L'Heureux
authors.forename: Ahmad
authors.initials: A
authors.lastname: Muinuddin
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Diamant
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D004594:Electrophysiology; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D005260:Female; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology
chemical_list: D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D001285:Atropine