title: Effect of L-arginine on endothelial injury and hemostasis in rabbit endotoxin shock.
abstract: To investigate whether impaired endothelial function was related to alteration of nitric oxide (NO) formation during endotoxic shock, we studied the effects of supplementation of L-arginine (L-Arg), D-arginine (D-Arg), and N(G)-nitro-L-arginine methyl ester (L-NAME), on endothelial function and structure in a rabbit model. Endotoxic shock was induced by a single lipopolysaccharide bolus (0.5 mg/kg i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor were determined by functional assays. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess damaged endothelial cell surface of the abdominal aorta. These parameters were studied 5 days after the onset of endotoxic shock and were compared under three conditions: in absence of treatment, with L-Arg or D-Arg supplementation, or with L-NAME. Both L-Arg and D-Arg significantly improved endothelium-dependent relaxation and endothelial morphological injury. L-NAME did not alter endothelial histological injury induced by lipopolysaccharide. These data indicate that arginine supplementation nonspecifically prevents endothelial dysfunction and histological injury in rabbit endotoxic shock. Moreover, L-Arg has no effect on coagulation activation and expression of monocyte tissue factor induced by endotoxic shock.
authors.affiliation: Department of Anesthesiology, Lille University Hospital, 59037 Lille, France.
authors.forename: E
authors.initials: E
authors.lastname: Wiel
authors.forename: Q
authors.initials: Q
authors.lastname: Pu
authors.forename: D
authors.initials: D
authors.lastname: Corseaux
authors.forename: E
authors.initials: E
authors.lastname: Robin
authors.forename: R
authors.initials: R
authors.lastname: Bordet
authors.forename: N
authors.initials: N
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Jude
authors.forename: B
authors.initials: B
authors.lastname: Vallet
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001784:Blood Gas Analysis; D000001:Calcimycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009000:Monocytes / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*; D013925:Thromboplastin / Q000032:analysis; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D015431:Weight Loss
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000001:Calcimycin; D013925:Thromboplastin; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester