MAST-CELLS MEDIATE ACID-INDUCED AUGMENTATION OF OPOSSUM ESOPHAGEAL BLOOD-FLOW VIA HISTAMINE AND NITRIC-OXIDE

Background & Aims: Increased esophageal blood flow during reflux episo des may play an important role in mucosal resistance to injury, althou gh the mechanism remains unclear. Decreased stainable mast cells and i ncreased luminal histamine release during acid exposure has been previ ously documented. Therefore, the role of mast cells, nerves, histamine , and nitric oxide in mediating increased blood flow during acid chall enge of the distal esophagus was investigated. Methods: The effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the neurotoxin tetrodetoxin, the histamine H-1 receptor antagonist promet hazine, and the NO synthase inhibitor N omega-nitro-F-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 blo od flow (P < 0.05). Disodium cromoglycate, promethazine, and N omega-n itro-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 mecha nism, plays a central role in the response of the esophageal microcirc ulation to luminal acid.