Involvement of platelet-activating factor in the hypotensive response to zymosan in rats

In anaesthetised rats, intravenous injection of zymosan induced a reduction of serum complement haemolytic activity, leukopenia, thrombocytopenia, a decrease in blood pressure, an increase in haematocrit and paw oedema. Stimulation of platelets resulted in their accumulation in lungs and liver as shown by the distribution of 51Cr-labelled platelets. The hypotensive response to zymosan was largely inhibited by WEB 2086, a PAF antagonist. Plasma extravasation was reduced by WEB 2086, by the association of mepyramine and methysergide with ketoprofen or BW 755C. Paw oedema was increased by ketoprofen and abolished by the association of WEB 2086, BW 755C, methysergide and mepyramine. This treatment did not modify the leukopenia. Lipopolysaccharide produced a decrease in blood pressure and, at higher doses, a reduction of serum complement haemolytic activity. It is concluded that the vascular responses to intravascular complement activation by zymosan in rats depend mainly on the release of PAF. They are also mediated, for a small part, by eicosanoids and mast cell amines. Though zymosan and endotoxin induced similar PAF-dependent effects, the complement system is not involved in endotoxin shock in rats.