Involvement of PAF-acether in the anaphylactic shock in the rat.
In normal Wistar rats, SDZ 63-675 (1.2 mg/kg) inhibited hypotension and hemoconcentration induced by PAF-acether (0.2-0.8 micrograms/kg.min). These effects of PAF-acether were not modified by ketoprofen (3 mg/kg). Only the hemoconcentration was reduced by BW755C (40 mg/kg). Part of the vascular effects of PAF-acether in rats would thus depend on the release of lipoxygenase products. In sensitized rats, SDZ 63-675 (1.2 mg/kg) increased the survival rate, reduced the vascular collapse and suppressed the hemoconcentration induced by intravenous injection of the antigen. BW755C (40 mg/kg) increased the survival rate and slightly reduced the vascular collapse. This anaphylactic shock was neither modified by ketoprofen (3 mg/kg), acetylsalicylic acid (100-200 mg/kg) and indometacin (3-6 mg/kg) nor by the association of methysergide (3 mg/kg), metiamide (35 mg/kg) and mepyramine (3 mg/kg). The inhibitory effect of SDZ 63-675 on the anaphylactic shock was not affected by the association with methysergide, mepyramine and metiamide or with indometacin. It was enhanced by acetylsalicylic acid. Injected simultaneously, SDZ 63-675 and BW755C suppressed the vascular collapse induced by the antigenic challenge. The main vasoactive factors responsible for this anaphylactic shock in the rat would thus be, in decreasing order, PAF-acether, leukotrienes and prostanoids. The association of mepyramine, methysergide and metiamide inhibited hypotension and hemoconcentration induced by the infusion of dextran. Since SDZ 63-675 had no influence on the effects of dextran, it is concluded that dextran did not release significant amounts of PAF-acether from mast cells.
Damas
J
J
Institut Léon Fredericq, Université de Liège, Belgium.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000707:Anaphylaxis / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D005260:Female; D007022:Hypotension / Q000517:prevention & control; D007660:Ketoprofen / Q000494:pharmacology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010972:Platelet Activating Factor; D011804:Quinolines; C053130:SRI 63-675; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D010047:Ovalbumin; D007660:Ketoprofen