Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.
The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002244:Carbon; D004396:Coloring Agents; D003543:Cysteamine / Q000494:pharmacology; D015237:Dinoprost; D000431:Ethanol / Q000037:antagonists & inhibitors; D005070:Evans Blue; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D007211:Indoles; D009942:Organometallic Compounds; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004396:Coloring Agents; D007211:Indoles; D009942:Organometallic Compounds; D011460:Prostaglandins F; C028433:chinese ink; D000431:Ethanol; C015445:copper phthalocyanine; D005070:Evans Blue; D003543:Cysteamine; D002244:Carbon; D015237:Dinoprost