Norepinephrine (NE) ; a standard of care, arginine vasopressin (AVP); an alternative candidate, and L-Canavanine (LC); a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and inocuity on global and regional hemodynamics, plasmatic and tissue lactate/pyruvate ratio (L/P), tissue high energy phosphate, renal function and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased (~ 35%) but aortic blood flow increased during endotoxin infusion (p<0.05 vs control). Additionally, there was a decrease in mesenteric and renal blood flows along with the regional to systemic ratio (p<0.05 vs control). All tested drugs were able to restore MAP to basal levels whereas they slightly decreased abdominal aortic flow. However, renal and mesenteric flow remained unchanged in experimental groups. Endotoxin significantly decreased diuresis and inulin clearance (~ 3- to 4-fold) whereas AVP or LC attenuated this drop (p<0.05 vs control). In contrast, NE did not improve endotoxin-induced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (p<0.05 vs control). Endotoxininduced gut hyperpermeability was inhibited by AVP, LC and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE (~ 2-fold increase) but not by AVP infusion (p<0.05 vs endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate and renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and lactate/pyruvate (L/P) ratio (~2- and 1.5-fold increases vs control, respectively), while AVP and LC, instead of NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function.