Y. Nishizaki et al., PROSTAGLANDIN E(2) ENHANCES GASTRIC DEFENSE-MECHANISMS AGAINST ACID INJURY IN UREMIC RATS, Gastroenterology, 107(5), 1994, pp. 1382-1389
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.