PAF increases vascular permeability in selected tissues: effect of BN-52021 and L-655,240.
The effect of the potent inflammatory mediator, platelet activating factor (PAF) was studied on the vascular permeability of selected rat tissues using the extravasation of Evans blue dye (EB) as a marker. EB (20 mg/kg) was injected in the caudal vein together with increasing doses of PAF (0.1, 1.0 and 5.0 micrograms/kg). The animals were killed and the dye was extracted in selected organs using formamide (4 ml/g wet weight tissues) and the content was expressed as EB micrograms/g dry weight. Extravasation of EB varied markedly from one tissue to another and increased as a function of time (from 0 to 60 min). PAF (5.0 micrograms/kg) increased the pancreas and duodenum vascular permeability by 15 and 5 fold respectively. At the doses of 0.1 and 1.0 microgram/kg, PAF induced a slight increase (P less than 0.01) of the vascular permeability of the heart 5 min after the injection. The PAF antagonist BN-52021 (2 and 10 mg/kg) produced a dose-dependent inhibition of the PAF effects on the pancreas, heart and duodenum. Maximum inhibition (approximately 100%) was achieved at the dose of 10 mg/kg. This antagonist given in the absence or the presence of PAF reduced the lung plasma extravasation below control levels. A thromboxane antagonist, L-655,240 (1.0 and 5.0 mg/kg) also inhibited PAF-induced increases in vascular permeability in heart, duodenum and pancreas. It also reduced below control levels the EB extravasation in kidneys, spleen and lungs. Maximum inhibition (50% for the duodenum, and 40% for the pancreas) was achieved at the dose of 5.0 mg/kg.
Sirois
M G
MG
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, P.Q., Canada.
Jancar
S
S
Braquet
P
P
Plante
G E
GE
Sirois
P
P
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004224:Diterpenes; D005070:Evans Blue / Q000493:pharmacokinetics; D046934:Ginkgolides; D007211:Indoles / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014018:Tissue Distribution
D004224:Diterpenes; D046934:Ginkgolides; D007211:Indoles; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D013931:Thromboxanes; C052517:L 655240; D005070:Evans Blue; C045856:ginkgolide B