The antidiuretic (V2) agonist,
dDAVP, stimulates release of the
clotting factors von Willebrand factor (vWF) and
factor VIIIc (FVIIIc) in humans. The objective of these studies was to identify and characterize
dDAVP stimulation of
clotting factor release in
pentobarbital-anesthetized rhesus monkeys using
V2 receptor agonists (
dDAVP,
SK&F 101926, SK&F 104146, SK&F 104244) and a
V2 receptor antagonist (
SK&F 105494) given i.v.
dDAVP (3.0 micrograms/kg) stimulated release of vWF, FVIIIc and
renin and was associated with
tachycardia and blood pressure-lowering activity. The
V2 receptor antagonist,
SK&F 105494 (30 micrograms/kg, i.v.), had no effect on
clotting factor release, heart rate or blood pressure, but prevented
dDAVP stimulation of
clotting factor release and
tachycardia. The V2 agonists
SK&F 101926, SK&F 104146 and SK&F 104244 did not stimulate
clotting factor release, blood pressure, heart rate or plasma
renin activity in this species at the doses tested. Thus, the rhesus monkey is a nonhuman primate species in which
dDAVP stimulation of FVIIIc and vWF occurs. The results support the hypothesis that
dDAVP stimulation of
clotting factor release is mediated by a low-affinity, V2-like receptor mechanism. The
tachycardia and
renin release associated with
dDAVP administration are most likely secondary to vasodilation, also mediated by a V2-like mechanism.