Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.
 BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects.
 In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively.
 In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs.
 - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs.
 325 +/- 46 sec, P less than .01).
 BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs.
 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs.
 60%, P less than .05).
 Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs.
 91 +/- 4 mm Hg, P less than .03).
 Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs.
 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs.
 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.
