Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsAC helped to design the study, collected the clinical information, directly analyzed the raw data, performed statistical analysis, drafted the paper, and contributed to the writing of the paper. BF helped to design the study and to include patients, participated with AC in the interpretation of all data, and contributed to the writing of the paper. BA and GMo helped to design the study, participated with AC in the interpretation of all data, and contributed to the writing of the paper. CaG, FP, and CM helped to perform the experiments. JC, AF, ChG, GMa, AV, and OM helped to include patients. All authors read and approved the final manuscript.AcknowledgementsThis work was supported by the Hospices Civils de Lyon.

We thank the technical staff of the immunology laboratory of Edouard Herriot University Hospital.
Arginine vasopressin (AVP) is recommended by the Surviving Sepsis Campaign to ‘be subsequently added to norepinephrine’ in volume- and catecholamine-refractory septic shock [1]. In the randomized, controlled, multicenter Vasopressin and Septic Shock Trial (VASST), however, AVP failed to reduce overall mortality as compared with norepinephrine among patients with septic shock [2].AVP represents a mixed V1a/V2 receptor (V1aR/V2R) agonist with a selectivity of 1:1 for each of these receptors. Whereas particular attention has been paid to the vasoconstriction mediated by vascular V1aRs [3,4], there is increasing evidence that stimulation of extrarenal (endothelial) V2Rs [5-7] may aggravate sepsis-induced vasodilation [4,8], fluid accumulation [9], leukocyte rolling [10], and microvascular thrombosis [11].

Against this background, selective V2R-antagonism potentially represents a new therapeutic approach in septic shock.We hypothesized that a first-line therapy with the selective V2R-antagonist (propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9) vasopressin [12,13] is more effective than infusion of placebo and AVP in restoring cardiovascular and renal functions in Brefeldin_A early ovine septic shock. Open-label norepinephrine was additionally titrated to maintain mean arterial pressure (MAP) in each group if necessary. Therefore, the present study was designed as a prospective, randomized, controlled, laboratory experiment to elucidate the effects of these treatment strategies on cardiopulmonary hemodynamics, mesenteric blood flow, global oxygen transport, acid-base balance, organ function, AVP plasma levels, oxidative stress, and mortality. The study hypothesis was tested in an established ovine model of fulminant septic shock resulting from generalized fecal peritonitis [14,15].