The mechanism of rat
thrombocytopenia induced by i.v.
injections of
platelet-activating factor (
PAF-acether) was investigated. Platelet counts performed after diluting the blood samples in 1%
formalin in saline showed that
PAF-acether (6 micrograms/kg i.v.) induced a significant
thrombocytopenia in rats, which peaked within 1 h, followed by a drastic increase of platelet counts at 4 h and a return to basal levels at 24 h. At this time, it was not possible to induce
thrombocytopenia with a second challenge with
PAF-acether, indicating a clear state of desensitization which disappeared within five days after the first injection of
PAF-acether. The pretreatment with the specific
PAF-acether receptor antagonist,
BN 52021 (2.5-15 mg/kg),
48740 RP (6-25 mg/kg) and
WEB 2086 (0.25-1 mg/kg) blocked the
thrombocytopenia dose dependently. The
lipoxygenase inhibitor nordihydroguaiaretic acid, at 25-100 mg/kg, was also effective against the
thrombocytopenia induced by
PAF-acether, reinforcing the potential involvement of
arachidonic acid derivatives in this process. Adrenal
hormones may modulate this process, since adrenalectomized animals responded to
PAF-acether with exacerbated
thrombocytopenia. No reduction in the platelet counts was noted when the blood was diluted in
formalin-free saline, indicating that unstable aggregates were formed in vivo, which tended to resolve in vitro. Our results suggest that the
thrombocytopenia induced in rats by PAF results from a reversible process of intravascular platelet aggregation, probably following the secretion of platelet-activating substances released by a first-hit blood cell.