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The Vasopressin Antagonist Sk&F 105494 Inhibits Desmopressin-Stimulated Clotting Factor Release in Vivo

  • Lewis B. Kinter
  • B. Thomas Goodwin
  • Irving McConnell
  • Sarah Campbell
  • William F. Huffman
  • Marie-Francoise Arthus
  • Michele Lonergan
  • Daniel G. Bichet
Part of the NATO ASI Series book series (NSSA, volume 242)

Abstract

The antidiuretic (V2) agonist, desmopressin (dDAVP), stimulates release of the clotting factors von Willebrand factor (vWF) and factor VIIIc (FVIIIc) in humans. dDAVP (3.0 μg/kg) stimulated release of vWF and FVIIIc, and was associated with hypotension and tachycardia in the pentobarbital-anesthetized rhesus monkeys (Macaca mulatta). The V2 receptor antagonist, SK&F 105494 (30 μg/kg), had no effect on clotting factor release, blood pressure or heart rate, but prevented dDAVP stimulation of clotting factor release, hypotension, and tachycardia. The results support the hypothesis that dDAVP stimulation of clotting factor release and vasodilation are mediated by low-affinity, V2-like receptor mechanisms.

Keywords

Rhesus Monkey Nephrogenic Diabetes Insipidus Vasopressin Receptor Vasopressin Antagonist Congenital Nephrogenic Diabetes Insipidus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Lewis B. Kinter
    • 1
    • 2
  • B. Thomas Goodwin
    • 1
    • 2
  • Irving McConnell
    • 1
    • 2
  • Sarah Campbell
    • 1
    • 2
  • William F. Huffman
    • 1
    • 2
  • Marie-Francoise Arthus
    • 1
    • 2
  • Michele Lonergan
    • 1
    • 2
  • Daniel G. Bichet
    • 1
    • 2
  1. 1.Departments of, Toxicology — U. S.(LBK)Laboratory Animal Science (IM, BTG, SC, and Peptidomimetic Research (WFH) SmithKline Beecham PharmaceuticalsKing of PrussiaUSA
  2. 2.Nephrology Research Service Hospital du Sacre-CoeurUniversity of Montreal (M-FA, ML, DGB)MontrealCanada

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