PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST ATTENUATES ENDOTOXIN-INDUCED VASCULAR HYPOREACTIVITY IN THE PITHED RAT

The role of platelet activating factor (PAF) and nitric oxide (NO) in the endotoxin-induced hyporeactivity to noradrenaline was studied in t he pithed rat. Presser dose-response curves to noradrenaline (0.01-10 mu g/kg, i.v.) were made starting 1 h after the administration of endo toxin (0.5 mg/kg, i.v.) to the rats. Saline was administered to the co ntrol rats. The PAF receptor antagonist, TCV-309 ethyl]carboxyl]ethyl] carbomoyl]-1-propylpyridinium nitrate, 100 mu g/kg, i.v.), or the NO s ynthase inhibitor, N-G-monomethyl-L-arginine(L-NMMA, 30 mg/kg, i.v.), was administered to the endotoxin-treated rats 20 or 10 min before the noradrenaline challenge. L-NMMA reversed endotoxin-induced hyporeacti vity completely. TCV-309 produced a significant, but partial attenuati on of the hyporeactivity to noradrenaline (P < 0.01). There was still significant hyporeactivity when compared with the control rats (P < 0. 01) and the L-NMMA-treated endotoxin-administered rats (P < 0.05). The se data suggest that endogenous PAF contributes to the vascular hypore activity to noradrenaline induced by endotoxin and that NO plays a maj or role in the endotoxin-induced hyporeactivity. (C) 1998 Elsevier Sci ence B.V.