Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via histamine and nitric oxide.
OBJECTIVE
Increased esophageal blood flow during reflux episodes may play an important role in mucosal resistance to injury, although the mechanism remains unclear. Decreased stainable mast cells and increased luminal histamine release during acid exposure has been previously documented. Therefore, the role of mast cells, nerves, histamine, and nitric oxide in mediating increased blood flow during acid challenge of the distal esophagus was investigated.


METHODS
The effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the neurotoxin tetrodotoxin, the histamine H1 receptor antagonist promethazine, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester were examined by monitoring opossum esophageal histamine release and blood flow during perfusion with 100 mmol/L HCl.


RESULTS
Luminal acid challenge significantly increased both histamine release and blood flow (P < 0.05). Disodium cromoglycate, promethazine, and N omega-nitro-L-arginine methyl ester attenuated the increase in blood flow to basal (saline-perfused) levels. Tetrodotoxin did not prevent an acute increase in blood flow that rapidly returned to baseline, likely from the ensuing hypotension.


CONCLUSIONS
These findings provide evidence that mast cell-derived histamine, acting through an NO-dependent mechanism, plays a central role in the response of the esophageal microcirculation to luminal acid.
Feldman
M J
MJ
Gastrointestinal Diseases Research Unit, Hotel Dieu Hospital, Kingston, Ontario, Canada.
Morris
G P
GP
Dinda
P K
PK
Paterson
W G
WG
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology; D004947:Esophagus / Q000098:blood supply* / Q000378:metabolism; D006632:Histamine / Q000502:physiology*; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008407:Mast Cells / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009893:Opossums; D011398:Promethazine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D009569:Nitric Oxide; D013779:Tetrodotoxin; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D011398:Promethazine; D004205:Cromolyn Sodium; D006851:Hydrochloric Acid; D019331:NG-Nitroarginine Methyl Ester