title: Unlike arginine vasopressin, the selective V1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor.
abstract: OBJECTIVE
  To compare the effects on von Willebrand factor release of the mixed vasopressin type 1a and type 2 receptor agonist arginine vasopressin and the selective vasopressin type 1a receptor agonist FE 202158, [Phe2,Ile3,Hgn4,Orn(iPr)8]vasopressin, at doses required for the treatment of septic shock.
  
  
  METHODS
  Prospective, randomized, controlled laboratory experiment.
  
  
  METHODS
  University animal research facility.
  
  
  METHODS
  Twenty-four chronically instrumented sheep.
  
  
  METHODS
  After a 5-day recovery from instrumentation, sheep were randomly assigned to receive a single intravenous bolus of the selective vasopressin type 2 receptor agonist desmopressin (1 nmol·kg(-1)) or continuous intravenous infusions of arginine vasopressin (3 pmol·kg(-1)·min(-1)), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol·kg(-1)·min(-1)), or vehicle (0.9% NaCl) (n = 6 each).
  
  
  RESULTS
  The von Willebrand factor antigen activity relative to hemoglobin concentration (vWF:Ag/Hb ratio) was measured at different time points during the 120-min study period. Maximal vWF:Ag/Hb ratio expressed as percentage of baseline level was significantly increased compared to vehicle-infused animals (3 ± 2%) in the desmopressin (40 ± 6%, p < .001) and arginine vasopressin groups (25 ± 4%, p < .001). The ratio for the FE 202158 group was not statistically different from the sham group (9 ± 2%, p = .208). Notably, maximal vWF:Ag/Hb ratio was lower in the FE 202158 than the arginine vasopressin group (p < .005).
  
  
  CONCLUSIONS
  Unlike the mixed vasopressin type 1a receptor/vasopressin type 2 receptor agonist arginine vasopressin, the selective vasopressin type 1a receptor agonist FE 202158 does not release von Willebrand factor. Because von Willebrand factor is involved in coagulatory and inflammatory pathways during septic shock, future studies should clarify the role of the vasopressin type 2 receptor-mediated von Willebrand factor increase by arginine vasopressin and the potential benefit of selective vasopressin type 1a receptor-agonists like FE 202158.
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA. Sebastian.Rehberg@ukmuenster.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rehberg
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Janina
authors.initials: J
authors.lastname: Rehberg
authors.forename: Erin
authors.initials: E
authors.lastname: La
authors.forename: Nicky
authors.initials: N
authors.lastname: Ferdyan
authors.forename: Steve
authors.initials: S
authors.lastname: Qi
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wisniewski
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Schteingart
authors.forename: Pierre J M
authors.initials: PJ
authors.lastname: Rivière
authors.forename: Régent
authors.initials: R
authors.lastname: Laporte
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D011446:Prospective Studies; D011897:Random Allocation; D017483:Receptors, Vasopressin / Q000819:agonists*; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy; D014667:Vasopressins / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism*
chemical_list: D017483:Receptors, Vasopressin; C029417:Von Willebrand antigen; C559490:vasopressin, Phe(2)-Ile(3)-Hgn(4)-Orn(iPr)(8)-; D014841:von Willebrand Factor; D014667:Vasopressins; D001127:Arginine Vasopressin