Gastric microvascular endothelium: a major target for aspirin-induced injury and arachidonic acid protection. An ultrastructural analysis in the rat.
Exposure of the gastric mucosa to aspirin results in exfoliation of the surface epithelium and deep mucosal necrosis. We assessed the changes in the mucosal microvessels during aspirin-induced injury and arachidonic acid protection of the gastric mucosa using transmission electron microscopy. Male Sprague-Dawley rats received intragastric pretreatment with either solubilizer (control) or detergent solubilized arachidonic acid (148 mg kg-1). One hour later 1-ml suspension of 200 mg kg-1 body weight acidified aspirin was administered intragastrically. The ultrastructure of mucosal microvasculature was assessed at 15 min and 4 h after aspirin administration both qualitatively and quantitatively by determining the number of necrotic or damaged capillaries in standardized mucosal sections. In addition, mucosal specimens were immunostained with a specific antiserum against vimentin, an endothelial marker, and fluorescence intensity was measured with a Nikon FX microscopic photometric system. In control rats, aspirin produced significant damage to both superficial and deeper microvessels consisting of: rupture of capillary walls, necrosis of endothelial cells, damage to endothelial organelles, deposition of fibrin and adherence of platelets to damaged endothelium. Vimentin fluorescence was reduced three-fold. Microvascular injury preceded the development of deep necrotic lesions. Microvascular damage and deep mucosal necrosis were significantly reduced by arachidonic acid pretreatment. We conclude that gastric mucosal microvessels are the major target for aspirin-induced injury and arachidonic acid protection.
Tarnawski
A
A
Department of Veterans Affair Medical Center, Long Beach, California 90822.
Stachura
J
J
Gergely
H
H
Hollander
D
D
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000627:therapeutic use*; D001241:Aspirin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D014746:Vimentin / Q000032:analysis
D001095:Arachidonic Acids; D014746:Vimentin; D016718:Arachidonic Acid; D001241:Aspirin