Unlike arginine vasopressin, the selective V 1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor

Sebastian Rehberg, Perenlei Enkhbaatar, Janina Rehberg, Erin La, Nicky Ferdyan, Steve Qi, Kazimierz Wisniewski, Lillian D. Traber, Claudio D. Schteingart, Pierre J M Rivière, Régent Laporte, Daniel L. Traber

Research output: Contribution to journalArticle

13 Citations (Scopus)

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, [Phe 2,Ile 3,Hgn 4,Orn(iPr) 8]vasopressin, at doses required for the treatment of septic shock. Design: Prospective, randomized, controlled laboratory experiment. Setting: University animal research facility. Subjects: Twenty-four chronically instrumented sheep. Interventions: 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), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol•kg -1•min), or vehicle (0.9% NaCl) (n = 6 each). Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)1957-1960
Number of pages4
JournalCritical Care Medicine
Volume40
Issue number6
DOIs
StatePublished - Jun 2012

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Vasopressin Receptors
Arginine Vasopressin
von Willebrand Factor
Deamino Arginine Vasopressin
Septic Shock
Sheep
Phe(2)-Ile(3)-Hgn(4)-Orn(iPr)(8)-vasopressin
Intravenous Infusions
Hemoglobins

Keywords

  • blood coagulation
  • peptide hormones
  • vasopressin V receptor
  • vasopressin V receptor
  • vasopressor
  • von Willebrand factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Unlike arginine vasopressin, the selective V 1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor. / Rehberg, Sebastian; Enkhbaatar, Perenlei; Rehberg, Janina; La, Erin; Ferdyan, Nicky; Qi, Steve; Wisniewski, Kazimierz; Traber, Lillian D.; Schteingart, Claudio D.; Rivière, Pierre J M; Laporte, Régent; Traber, Daniel L.

In: Critical Care Medicine, Vol. 40, No. 6, 06.2012, p. 1957-1960.

Research output: Contribution to journalArticle

Rehberg, S, Enkhbaatar, P, Rehberg, J, La, E, Ferdyan, N, Qi, S, Wisniewski, K, Traber, LD, Schteingart, CD, Rivière, PJM, Laporte, R & Traber, DL 2012, 'Unlike arginine vasopressin, the selective V 1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor', Critical Care Medicine, vol. 40, no. 6, pp. 1957-1960. https://doi.org/10.1097/CCM.0b013e31824e0fe5
Rehberg, Sebastian ; Enkhbaatar, Perenlei ; Rehberg, Janina ; La, Erin ; Ferdyan, Nicky ; Qi, Steve ; Wisniewski, Kazimierz ; Traber, Lillian D. ; Schteingart, Claudio D. ; Rivière, Pierre J M ; Laporte, Régent ; Traber, Daniel L. / Unlike arginine vasopressin, the selective V 1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor. In: Critical Care Medicine. 2012 ; Vol. 40, No. 6. pp. 1957-1960.
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T1 - Unlike arginine vasopressin, the selective V 1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor

AU - Rehberg, Sebastian

AU - Enkhbaatar, Perenlei

AU - Rehberg, Janina

AU - La, Erin

AU - Ferdyan, Nicky

AU - Qi, Steve

AU - Wisniewski, Kazimierz

AU - Traber, Lillian D.

AU - Schteingart, Claudio D.

AU - Rivière, Pierre J M

AU - Laporte, Régent

AU - Traber, Daniel L.

PY - 2012/6

Y1 - 2012/6

N2 - 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, [Phe 2,Ile 3,Hgn 4,Orn(iPr) 8]vasopressin, at doses required for the treatment of septic shock. Design: Prospective, randomized, controlled laboratory experiment. Setting: University animal research facility. Subjects: Twenty-four chronically instrumented sheep. Interventions: 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), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol•kg -1•min), or vehicle (0.9% NaCl) (n = 6 each). Measurements and Main 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.

AB - 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, [Phe 2,Ile 3,Hgn 4,Orn(iPr) 8]vasopressin, at doses required for the treatment of septic shock. Design: Prospective, randomized, controlled laboratory experiment. Setting: University animal research facility. Subjects: Twenty-four chronically instrumented sheep. Interventions: 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), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol•kg -1•min), or vehicle (0.9% NaCl) (n = 6 each). Measurements and Main 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.

KW - blood coagulation

KW - peptide hormones

KW - vasopressin V receptor

KW - vasopressin V receptor

KW - vasopressor

KW - von Willebrand factor

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