title: Evidence for a direct effect on vascular permeability of platelet-activating factor induced hemoconcentration in the guinea pig.
abstract: The ability of synthetic platelet-activating factor (PAF) given intravenously to produce loss (extravasation) of protein rich plasma (resulting in hemoconcentration) has been examined using guinea pigs. Hemoconcentration induced by PAF was not prevented by prior administration of inhibitors of thromboxane synthetase (7-(3-pyridyl)heptanoic acid, UK-37,248-01), PGI2, aspirin, indomethacin or antiserum induced thrombocytopenia. Calcium channel blockers (nifedipine, verapamil, diethylamino octyltrimethoxybenzoate, diltiazem), antihistamines (pyrilamine, cimetidine, diphenhydramine), or the elevator of cAMP IBMX were ineffective in blocking PAF-induced hemoconcentration. In contrast, CV-3988, reported to be a specific antagonist to PAF, was 98% inhibitory of PAF extravasation when given i.a. at 3.5 mg/kg. The ED50 was 0.14 mg/kg I.A. and 15 mg/kg p.o. against 75 ng/kg PAF. These data suggest that PAF-induced hemoconcentration involves receptor mediated alterations of vascular permeability that are inhibited by a specific PAF antagonist.
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002199:Capillary Permeability; D006168:Guinea Pigs; D006400:Hematocrit; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D002121:Calcium Channel Blockers; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; D006632:Histamine; C037913:CV 3988; D013930:Thromboxane-A Synthase