16-16-dimethylprostaglandin-e2 and sodium-thiosulfate

Protection of the gastric mucosa may be the result of either increased cellular resistance to injury (cytoprotection) or, alternatively, decreased exposure of mucosal cells to the damaging agent. To determine whether decreased exposure of mucosal cells to damaging agents plays a role in mucosal protection by 16,16-dm PGE2 or sodium thiosulfate, we estimated the intramucosal concentration of 22NaCl and measured its absorption from the gastric lumen into the systemic circulation 1 and 5 min after intragastric administration of hypertonic (25% w/v) 22NaCl. In an attempt to explain the differences observed, we also measured the net transmucosal water flux in control animals and rats pretreated with the protective agents. Administration of hypertonic NaCl rapidly (within 1 min) induced extensive hemorrhagic mucosal lesions that were significantly reduced by pretreatment with 16,16-dm PGE2 or sodium thiosulfate. Ultra-low temperature autoradiography indicated that luminal hypertonic 22NaCl penetrates the upper layers of the mucosa in relatively high concentrations (12.5% w/v) within 1 min but its concentration decreases rapidly and reached low levels (3.12% w/v) by 5 min. Absorption of NaCl from the gastric lumen into the systemic circulation 1 and 5 min after hypertonic NaCl was lower in both pretreatment groups than in the control. Net gastric transmucosal water flux (from serosa to mucosa) increased (P less than 0.05) from 100 +/- 2 in controls, to 1470 +/- 8 and 715 +/- 9 microliters in rats pretreated with 16,16-dm PGE2 and sodium thiosulfate, respectively. We conclude that 16,16-dm PGE2 and sodium thiosulfate protect the gastric mucosa against hypertonic NaCl, diminish mucosal penetration of NaCl, decrease mucosal absorption of NaCl, and significantly increase serosal to mucosal transmucosal water flux.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 16,16-Dimethylprostaglandin E2; Animals; Antioxidants; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Sodium Radioisotopes; Thiosulfates; Time Factors

We used in vivo microscopy and laser-Doppler velocimetry to examine the effects on the gastric mucosal microcirculation and in gastric mucosal blood flow of agents that induce acute gastric mucosal damage. In vivo microscopic observation of superficial mucosal capillaries revealed vascular stasis within a mean of 54, 81, or 61 s after 100% ethanol, 0.6 N HCl, or 0.2 N NaOH, with the subsequent development of hemorrhagic mucosal lesions. Mucosal blood flow estimated by laser-Doppler velocimetry decreased by 30% at 5 min after luminal application of 100% ethanol, and decreased further to about 40% of basal levels by 15 min. The decreased mucosal blood flow 15 min after application of 50% ethanol correlated with the extent of hemorrhagic mucosal lesions. Examination of the submucosal vessels that supply and drain the mucosa showed moderate dilation of small arterioles 1, 3, and 6 min after exposure to 100% ethanol but there were no consistent changes in venules. Mild vasoconstriction of small- and medium-sized venules could be detected 6, 10, and 15 min after NaOH but not after exposure to HCl. Pretreatment with 16,16-dimethyl prostaglandin E2 or sodium thiosulfate before exposure of the mucosa to ethanol prevented capillary stasis, maintained mucosal blood flow, and prevented the development of hemorrhagic gastric mucosal lesions. Topical mucosal application of 16,16-dimethyl prostaglandin E2 decreased, whereas topical exposure to sodium thiosulfate increased gastric mucosal blood flow, indicating that change in blood flow per se is an unlikely mediator of protection.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Capillaries; Ethanol; Female; Gastric Mucosa; Hemorrhage; Hydrochloric Acid; Microcirculation; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Regional Blood Flow; Rheology; Sodium Hydroxide; Stomach Diseases; Thiosulfates