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

To investigate whether impaired endothelial function was related to alterat ion of nitric oxide (NO) formation during endotoxic shock, we studied the e ffects of supplementation of L-arginine (L-Arg), D-arginine (D-Arg), and NG -nitro-L-arginine methyl ester (L-NAME), on endothelial function and struct ure in a rabbit model. Endotoxic shock was induced by a single lipopolysacc haride bolus (0.5 mg/kg iv, Escherichia coli endotoxin). Coagulation factor s and expression of monocyte tissue factor were determined by functional as says. Endothelium-dependent vascular relaxation was assessed by in vitro va scular reactivity. Immunohistochemical staining (CD31) was performed to ass ess damaged endothelial cell surface of the abdominal aorta. These paramete rs 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 suppl ementation, or with L-NAME. Both L-Arg and D-Arg significantly improved end othelium-dependent relaxation and endothelial morphological injury. L-NAME did not alter endothelial histological injury induced by lipopolysaccharide . These data indicate that arginine supplementation nonspecifically prevent s 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.