Ethanol-induced jejunal microvascular and morphological injury in relation to histamine release in rabbits.

BACKGROUND: To investigate the relation between ethanol-induced jejunal microvascular injury, morphological changes, and histamine release, the present study examined whether the attenuation of microvascular effect of ethanol by 16,16-dimethyl prostaglandin E2 (dmPGE2) (reported by us previously) was associated with an attenuation of epithelial damage and histamine release. METHODS: Rabbits were used. Mucosal microvascular injury was assessed by determining jejunal plasma protein loss (JPPL), histamine release by measuring histamine concentration of the gut effluent, and epithelial damage by routine histology. RESULTS: (1) During 90-minute jejunal ethanol perfusion, there was a direct relation between the time course of histamine release and that of JPPL. (2) dmPGE2 attenuated the ethanol-induced JPPL and histamine release, and the decrease in JPPL was directly proportional to the decrease in histamine release. (3) dmPGE2 did not alleviate ethanol-induced epithelial damage. (4) Ketotifen (a mast cell stabilizer), similar to dmPGE2, attenuated ethanol-induced JPPL and histamine release. (5) Ethanol caused histamine release by the jejunum in vitro; this was attenuated by dmPGE2 and also by phloretin (a mast cell stabilizer). CONCLUSIONS: It appears that (1) ethanol causes JPPL by inducing release of mediators from mucosal mast cells. (2) dmPGE2 attenuates JPPL by stabilizing mast cells. (3) The ethanol-induced mucosal microvascular injury is directly related to histamine release but not to epithelial damage.

Mucosal secretion and cytoprotection of the rat gastric mucosa.

We carried out a series of experiments to test the hypothesis that many examples of gastric cytoprotection result from the ability of protective agents to elevate mucosal secretion. Specifically, such protection would be effective against barrier breakers that act directly on the mucosal surface. We have previously observed that the protection found to result, in our rat gastric chamber model, from luminal stasis or from sucralfate, was accompanied by increases in the thickness of a juxtamucosal pH gradient. The pH gradient was measured with antimony microelectrodes and was about 900 microns thick over chambered gastric mucosae that had not had the luminal solution stirred for at least 5 min. When the solution was stirred (200 rpm) for 10 min with a plastic paddle, the thickness of the pH gradient was decreased to about 400 microns but recovered to more than 90% of the starting value within 5 min. The thickness of the pH gradient varied from site to site, with a range from about 500 microns to 1,800 microns. However, the thickness was constant at a given site when it was remeasured after about 1 h. Capsaicin at a concentration of 640 microM rapidly increased both gastric blood flow and the thickness of the juxtamucosal pH gradient by about 50%. However, 25 min after removal of the capsaicin the gastric blood flow approached pre-capsaicin levels, and the thickness of the gradient remained increased by nearly 50%. In a third set of experiments, the vulnerability of specific sites on the chambered mucosae to acidified sodium taurocholate was correlated with the thickness of the juxtamucosal pH gradient before exposure to taurocholate.(ABSTRACT TRUNCATED AT 250 WORDS)