Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.
Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.
Sandler
A D
AD
Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City 52242.
Schlegel
J F
JF
DeSautel
M G
MG
Maher
J W
JW
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000502:physiology*; D004285:Dogs; D004947:Esophagus / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D011312:Pressure; D011674:Pulse / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D014628:Vagotomy
D006584:Hexamethonium Compounds; D010880:Piperidines; D013373:Substance P; D018738:Hexamethonium; D013779:Tetrodotoxin; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002211:Capsaicin