Effect of L-arginine on endothelial injury and hemostasis in rabbit endotoxin shock.
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.
Wiel
E
E
Department of Anesthesiology, Lille University Hospital, 59037 Lille, France.
Pu
Q
Q
Corseaux
D
D
Robin
E
E
Bordet
R
R
Lund
N
N
Jude
B
B
Vallet
B
B
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
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