PROSTAGLANDIN E(2) ENHANCES GASTRIC DEFENSE-MECHANISMS AGAINST ACID INJURY IN UREMIC RATS

Background/Aims: Uremia increases gastric mucosal H+ permeability and acid back-diffusion-related injury in rats. The aim of this study was to examine the effect of the synthetic gastroprotective compound 16,16 -dimethyl prostaglandin E(2) (16,16-dm PGE(2)) on the gastric barrier to acid injury in uremic rats. Methods: Chronic renal failure was indu ced by subtotal nephrectomy. Acid back-diffusion injury was induced by superfusion with 15% ethanol in 0.15N HCl and was assessed by image a nalysis. Intracellular pH, initial surface cell acidification rate, an d thickness of mucous gel layer were measured with in vivo microscopy. Gastric mucosal blood flow was measured in separate experiments by la ser-Doppler flowmetry. Results: Pretreatment with 16,16-dm PGE(2) atte nuated H+ back-diffusion and prevented the production of gross lesions . 16,16-dm PGE(2) increased gastric mucous gel thickness, decreased in itial acidification rate, and maintained intracellular pH homeostasis during exposure to luminal acid. Gastric mucosal blood flow was not ch anged during superfusion with a neutral buffer but increased during ac id exposure in rats treated with 16,16-dm PGE(2). Conclusions: 16,16-d m PGE(2) attenuated H+ back-diffusion injury in uremic rats. This effe ct was associated with blunting of the initial decrease of intracellul ar pH and enhanced surface cell intracellular pH homeostasis during ac id exposure. These effects were associated with an increased mucous ge l layer thickness and an acid-related increase in blood flow.