Platelet activating factor and systemic anaphylaxis in Nippostrongylus brasiliensis-sensitized rats: differential effects of PAF antagonists.
1. The effects of two platelet-activating factor (PAF) antagonists, WEB 2086 and BN 52021, in reducing the changes in extravasation (Evans blue technique) and blood flow (radiolabelled microsphere method) to various organs and tissues following anaphylactic shock in the Nippostrongylus brasiliensis-sensitized rat were investigated. 2. Both antagonists attenuated anaphylaxis-induced increases in plasma protein leak in the trachea, stomach and small intestine, although they did not block extravasation in the colon and kidneys. 3. Anaphylaxis-induced decreases in blood flow to the adrenals were effectively antagonized by WEB 2086, although this antagonist did not reverse blood flow decreases to any other tissues. BN 52021, on the other hand, did not alter anaphylaxis-induced decreases in blood flow to the adrenals, but effectively prevented dramatic decreases in blood flow to the large and small bowel and spleen. 4. Anaphylactic shock produced marked reduction in blood pressure that was partly reversed by WEB 2086, whereas BN 52021 effectively blocked the decreases in cardiac output. 5. Thus, PAF is responsible for some of the haemodynamic and extravasation of protein changes associated with systemic anaphylaxis in the rat, although the differential inhibition observed with the two antagonists suggests that PAF alters vascular responsiveness through different mechanisms in selected tissues.
Mathison
R
R
Department of Medical Physiology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Davison
J S
JS
Befus
A D
AD
D000707:Anaphylaxis / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D004224:Diterpenes; D005070:Evans Blue; D046934:Ginkgolides; D006439:Hemodynamics / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D009559:Nippostrongylus / Q000276:immunology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D001798:Blood Proteins; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D005070:Evans Blue; C045856:ginkgolide B