Electrophysiological and pharmacological responses of chronically denervated lower esophageal sphincter of the opossum.
OBJECTIVE
Achalasia is characterized by loss of myenteric neurons and incomplete relaxation of the lower esophageal sphincter (LES). The aim of this study was to develop an achalasia model in the opossum using the surfactant benzyldimethyltetradecylammonium chloride (BAC). This study further characterizes the achalasia model.


METHODS
BAC or saline was injected circumferentially into the LES of 14 adult opossums. Eight months after injection, manometry, isolated muscle bath studies, electrical field stimulation, and histochemical analysis were performed.


RESULTS
Manometrically, the LES of BAC-treated opossums showed higher pressures (38.7 +/- 12 mm Hg vs. 17 +/- 3.0 mm Hg) and reduced esophageal body contraction amplitudes (4.2 +/- 3 mm Hg vs. 27.4 +/- 12 mm Hg). Isolated muscle strips challenged with carbachol and sodium nitroprusside contracted and relaxed similarly to controls. Electrical field stimulation failed to induce relaxation in BAC-treated tissue but did induce contraction. Contractile responses were markedly reduced by tetrodotoxin and atropine in BAC-treated animals and controls. An altered nitric oxide system was shown by the lack of response to L-arginine and N omega-nitro-L-arginine. Histology showed loss of myenteric neurons and increased cholinergic nerve bundles.


CONCLUSIONS
Loss of NO inhibitory myenteric neurons markedly reduces the relaxation of the LES, and histology and pharmacological responses suggest a proliferation of cholinergic nerves into the LES contributing to the static elevated pressures of the amyenteric LES.
Gaumnitz
E A
EA
Department of Medicine, University of Wisconsin-Madison, USA.
Bass
P
P
Osinski
M A
MA
Sweet
M A
MA
Singaram
C
C
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001548:Benzalkonium Compounds; D002799:Cholinergic Fibers / Q000187:drug effects; D003714:Denervation; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D004931:Esophageal Achalasia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004943:Esophagogastric Junction / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008365:Manometry; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009893:Opossums; D011312:Pressure; D013779:Tetrodotoxin / Q000494:pharmacology
D001548:Benzalkonium Compounds; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; D001120:Arginine