Splanchnic vascular endothelial dysfunction in rat endotoxemia: role of superoxide radicals.
Intravenous lipopolysaccharide, 30 mg/kg, results in rapid systemic hypotension in anesthetized rats. Interaction of lipopolysaccharide with the vascular endothelium and blood borne cells results in the elaboration of cytokines and oxygen-derived free radicals, all of which can be injurious to normal endothelial function. To evaluate endothelial function, superior mesenteric artery rings were isolated from endotoxemic rats just prior to death. Endotoxemia significantly blunted superior mesenteric artery ring vasorelaxations to acetylcholine and to A23187 but not to NaNO2. Contraction of superior mesenteric artery rings from endotoxemic rats induced by U46619 was not altered. Treatment with human superoxide dismutase or U74006F, an aminosteroid, significantly preserved vasorelaxation to acetylcholine and A23187. However, the hydroxyl radical scavenger N-(2-mercaptopropionyl)-glycine did not protect the endothelium. Thus, intravenous lipopolysaccharide can induce endothelial dysfunction in superior mesenteric artery rings. Furthermore, because superoxide dismutase but not N-(2-mercaptopropionyl)-glycine preserves endothelial function, it is likely that superoxide radicals mediate the endothelial dysfunction observed in endotoxemic rats.
Siegfried
M R
MR
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Ma
X L
XL
Lefer
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004731:Endotoxins / Q000097:blood*; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D011281:Pregnatrienes / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D008625:Tiopronin / Q000494:pharmacology
D004731:Endotoxins; D005609:Free Radicals; D011281:Pregnatrienes; D011450:Prostaglandin Endoperoxides, Synthetic; D013481:Superoxides; D000001:Calcimycin; D008625:Tiopronin; D013482:Superoxide Dismutase; D012977:Sodium Nitrite; D000109:Acetylcholine; C053355:tirilazad