Role of endogenous acid in gastric mucosal injury induced by local ischemia-reperfusion in the rat.
The role of endogenous acid was evaluated in a rat model of gastric epithelial damage induced by local ischemia-reperfusion (IR). Because no gross lesion was induced in this model, the damage was quantified by measuring the blood-to-lumen [51Cr]EDTA clearance. A proton pump inhibitor (omeprazole) or an H2-receptor antagonist (T-593) was used to suppress luminal acidity from pH 5 to pH 6.3-7.0. Both drugs significantly attenuated the increase in clearance induced by IR, indicating an important role for endogenous acid. A second series of experiments was performed to confirm whether the change in pH from around 5 to 7 was sufficient to reduce IR-induced gastric mucosal damage. Phosphate-buffered saline was perfused into the gastric lumen to neutralize the endogenous luminal acid. Although the luminal acid was completely neutralized, no reduction in clearance was observed. These data indicate that endogenous luminal acid does not play an important role in gastric injury induced by local IR stress and that a proton pump inhibitor or H2-receptor antagonist may suppress IR injury by a mechanism other than reducing luminal acidity, i.e., reducing consumption of ATP needed for acid secretion, thereby improving gastric mucosal energy metabolism.
Seno
K
K
First Department of Internal Medicine, Nagoya City University, Japan.
Joh
T
T
Yokoyama
Y
Y
Itoh
M
M
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D013450:Sulfones / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006146:Guanidines; D006635:Histamine H2 Antagonists; D013450:Sulfones; C088837:T 593; D009853:Omeprazole