A “Histodilutional Barrier” Formed in Gastric Mucosa by VEGF Pretreatment Protects Ethanol‐Induced Hemorrhagic Gastric Erosions in Rats

Abstract

Since VEGF increases vascular permeability (VP), we tested the hypothesis that it might create a perivascular “histodilutional barrier”, like histamine, hence delay the absorption of damaging chemicals.MethodsFasted Sprague‐Dawley rats were given VEGF164 (0.01, 0.04, or 0.2 ug/100g) by gavage either alone or 30 min before administration of 75% ethanol (1 ml/kg). Evans blue was injected i.v. 15 min before autopsy. Rats were euthanized 30 min after VEGF alone or 1 hr after ethanol administration. Scrapings of gastric mucosa were harvested for VP measurement spectrophotometrically (560 nm) of Evans blueextravasation in the gastric mucosa. Hemorrhagic gastric mucosal lesions were measured by an Imaging Analysis System and calculated as % of glandular stomach, and also examined by histology.Results0.04ug/100g VEGF treatment significantly increased gastric VP compared to the controls (p < 0.05). Pretreatment with 0.01, 0.04, or 0.2 ug/100g VEGF reduced ethanol‐induced lesions from 10.6±1.7% (controls) to 8.9±1.8, 0.9±0.2 (p <0.01), or 2.8±0.7% (p <0.05), respectively. Histologic examination showed mild or moderate gastric edema in lamina propria or submucosa after VEGF alone, and no or only superficial gastric erosions in the rats treated with VEGF + ethanol.Conclusions1) Pretreatment with VEGF offered dose‐dependent gastroprotection in rats exposed to ethanol. 2) The likely mechanisms might be related to a histodilutional barrier induced by VEGF. 3) Further studies are needed to elucidate the molecular mechanisms of this new form of gastroprotection.(Supported by VA Merit Review Grants to S. Szabo).