Effects of endothelin on the lethality induced by platelet-activating factor or endotoxin in the mouse

Platelet-activating factor (PAF) is a mediator that decreases cardiac output and total peripheral resistances leading to profound hypotension. It seems to be involved in shock states and in the deleterious effects of endotoxin. As the natural peptide endothelin (ET) shows potent vasoconstrictor properties, we evaluate its activity towards PAF and endotoxin-induced lethality in mice. ET, at doses which per se did not exert any effects on mice vitality, produced a dose-dependent decrease in the PAF-induced lethality with a total protection at 5 micrograms/kg. But conversely to these results, ET potentiated the mortality induced by endotoxin. These results suggest that ET or endothelin analogs could be worthy for therapeutic use in some types of shock, at least when endotoxin is not involved. Complementary studies are necessary to strengthen these preliminary results.