Serosal bicarbonate protects against acid injury to rabbit esophagus

The role of serosal bicarbonate ions (HCO₃ ^-) in protection against acid injury was investigated in rabbit esophageal mucosa mounted in Ussing chambers. Luminal acidification reduced potential difference and resistance in tissues exposed serosally to HCO₃ ^- or (unbuffered) HCO₃-free solution. Whereas resistance declined similarly in both groups, potential difference declined less in HCO₃ ^- solution. After washout, HCO₃-bathed tissues also had a greater increase in resistance, lower permeability to mannitol, and less histologic damage. Furthermore, as protection by HCO₃ ^- was not blocked by pretreatment with either the anion exchange blocker, 4 acetamido-4′-isothiocyanatostilbene 2-2′-disulfonic acid, or the carbonic anhydrase inhibitor, acetazolamide, and replacement of HCO₃ ^- with N-2-hydroxy-ethylpiperazine-N′-2-ethane sulfonic acid, a buffer impermeant to cells, was protective, an extracellular site for protection by HCO₃ ^- was likely. Where in the extracellular space HCO₃ ^- buffers H⁺ is unclear, but the absence of change in luminal pH and the inability to prevent the acid-induced increase in permeability in HCO₃-bathed tissues argue against a luminal (preepithelial) site. Also, rapid repair was not demonstrated, indicating that a luminal site for protection after surface cell damage was unlikely. We conclude that serosal HCO₃ ^- is important in esophageal protection against acid damage by buffering H⁺ within the intercellular compartment of the extracellular space.