Journal of Applied Physiology
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J Appl Physiol 89: 1811-1818, 2000;
8750-7587/00 $5.00
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Vol. 89, Issue 5, 1811-1818, November 2000

Effect of L-arginine on endothelial injury and hemostasis in rabbit endotoxin shock

Eric Wiel1, Qian Pu2, Delphine Corseaux3, Emmanuel Robin1, Régis Bordet2, Niels Lund4, Brigitte Jude3, and Benoît Vallet1

Departments of 1 Anesthesiology, 2 Pharmacology, and 3 Hematology, Lille University Hospital, 59037 Lille, France; and 4 Department of Anesthesiology, University of Rochester, Rochester, New York 14642

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 NG-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 iv, 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.

endothelium; endotoxic shock; lipopolysaccharide; NG-nitro-L-arginine methyl ester; tissue factor; monocyte


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