VASCULAR-RESPONSES OF PLATELET-ACTIVATING-FACTOR IN THE CEBUS-APELLA PRIMATE AND INHIBITORY PROFILES OF ANTAGONISTS SRI 63-072 AND SRI 63-119

We have evaluated several effects of intravenous administration of synthetic platelet-activating factor (PAF) in the nonhuman primate Cebus apella. Parameters measured were hemoconcentration (monitored by changes in hematocrit), thrombocytopenia (platelet counts), leukopenia (loss of buffy coat), bronchoconstriction (increased airway resistance to fixed airway ventilation), thromboxane A2 production (radioimmunoassay to thromboxane B2) and in vitro aggregation responses of platelets in platelet-rich plasma. Cebus platelets were refractory to PAF-induced aggregation (up to 50 .mu.M) and there was no evidence of thrombocytopenia, elevated thromboxane B2 levels, loss of buffy coat or bronchoconstriction following systemic PAF injection. Animals exhibited reproducible but varying sensitivities to PAF-induced hemoconcentration, where 3.5-30 .mu.g/kg PAF (6.6-57 nmol/kg) was required to produce 28-32% increased hematocrit range for the colony. Hemoconcentration induced by PAF in baboons and rhesus occurred at similar doses, suggesting comparable sensitivity. Prior administration of PAF receptor antagonists SRI 63-072 or SRI 63-119 at 3 mg/kg inhibited cebus hemoconcentration responses to 3.5 .mu.g/kg PAF by 96% and 100%, respectively. The ED50 values were 0.95 and 0.60 mg/kg, respectively. These results suggest that the cebus exhibits a producible hemoconcentration effect to PAF and that these vascular responses can be inhibited by a PAF receptor antagonist.