H+ back diffusion interferes with intrinsic reactive regulation of esophageal mucosal blood flow.
The esophageal mucosa maintains a barrier that is relatively impermeable to glucose, H+, and other small molecules. Injury of the mucosa causes disruption of this barrier, manifest initially by increased permeability to small molecules. In the stomach the mucosa is protected from gross ulceration in the presence of bile-induced H+ back diffusion (JH+) by increases in mucosal blood flow (Qm). Qm to the esophagus during injury has never been studied. We explored the possibility that esophageal Qm would increase as a compensatory reaction to early barrier disruption. Rabbits (2 to 4 kg) were anesthetized and the in situ esophagus was luminally perfused for two 1-hour periods with subulcerogenic concentrations of bile salts, pepsin, or trypsin in the presence (pH 2) or absence (pH 7) of acid. Qm was measured with 15 mu radioactive microspheres in nine experimental groups with a total of 62 rabbits. Changes in Qm were compared with changes in permeability of the esophageal barrier to glucose, Na+, and H+. When the mucosal barrier was broken by bile salts or trypsin at a neutral pH, no acid back diffusion occurred and barrier disruption was accompanied by dramatic increases in esophageal mucosal blood flow. In contrast, barrier disruption by bile salts, pepsin, or acid during pH 2 perfusions failed to elicit increases in Qm when significant JH+ (50 microEq/hr) occurred. These results demonstrate a loss in reactive regulation of esophageal Qm in the presence of significant JH+ that may contribute to the injury seen in acid reflux esophagitis.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002302:Cardiac Output; D004058:Diffusion; D004942:Esophagitis, Peptic / Q000503:physiopathology*; D004947:Esophagus / Q000098:blood supply* / Q000378:metabolism; D005744:Gastric Acid / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D009092:Mucous Membrane / Q000098:blood supply / Q000378:metabolism; D010539:Permeability; D011652:Pulmonary Circulation; D011817:Rabbits; D012039:Regional Blood Flow; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology
D001647:Bile Acids and Salts; D006859:Hydrogen; D012964:Sodium; D014357:Trypsin; D005947:Glucose