PAF increases vascular permeability in selected tissues: effect of BN-52021 and L-655,240

Abstract

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.