Gastric cytoprotection is secondary to increased mucosal fluid secretion: A study of six cytoprotective agents in the rat

We tested the hypothesis that rapidly developing gastric cytoprotection pro duced by topical application of exogenous compounds is a result of increase d gastric mucosal fluid secretion. Ex vivo gastric chambers were prepared i n rats which were subsequently exposed topically to one of the prostaglandi n (PG) E-1 analogues misoprostol or rioprostil, PGE,, nicotine, N-ethylmale imide (NEM), 0.25 M HCl, or to their respective vehicles. All agents were a dded to empty chambers to avoid complications resulting from dilution by ga stric contents. Effects of these agents on intraluminal volume changes, blo od flow, juxtamucosal pH, histology, and on the mucosal damage resulting fr om necrotizing agents were studied, All six agents were cytoprotective and each increased net secretion of fluid by the chambered mucosae. Gastric blo od flow was not significantly increased by NEM, by 0.25 M HCl, or by nicoti ne compared to controls, and the juxtamucosal pH was not significantly incr eased by any of the three agents for which this was studied. Vacuole format ion in surface epithelial cells and subepithelial edema were seen after exp osure to some agents, but none of the agents led to formation of a thick ba rrier of exfoliated cells and mucus. Ablation of primary afferent nerves wi th capsaicin abolished both protection by 0.25 M HCl and the net increase i n fluid secretion by the mucosae. Capsaicin ablation did not alter either t he protection afforded by NEM or the increase in volume of secretion. We co nclude that increased mucosal fluid secretion is the common factor present with all six cytoprotective agents and hence may be the predominant mechani sm of cytoprotection against topically applied necrotizing agents.