Antiinflammatory agents inhibit microvascular permeability induced by leukotrienes and by stimulated human neutrophils.
One pathologic change common to the inflammatory process is loss of microvessel membrane integrity which results in edema. Polymorphonuclear leukocytes (PMN) are primary contributors to the development of edema because they cause tissue injury which alters vascular permeability and hemodynamics. The aim of this study was to assess the influence of arachidonic acid metabolites generated by activation of human PMN on the in vivo microvascular preparation of the hamster cheek pouch. Fluorescein-labeled dextran MW: 150,000 was used to assess microvascular permeability. Human PMN were activated with arachidonic acid (AA) and the calcium ionophore A23187, and the supernatant retained for testing. Topical application of the PMN supernatant, purified LTD4 or LTB4 resulted in marked extravasation of macromolecules from post-capillary venules of control hamsters. The extravasation was reduced when hamsters were pretreated with indomethacin (5 mg/kg), imidazole (25 mg/kg), ketoconazole (10 mg/kg), 13-azaprostanoic acid (30 mg/kg), FPL 55712 (1 mg/kg) and dimethylthiourea (500 mg/kg). The interpretation of the results suggests that the increased vascular permeability induced by PMN secretions may be mediated in part by the thromboxane pathway.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply / Q000187:drug effects; D006224:Cricetinae; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013189:SRS-A / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005609:Free Radicals; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013928:Thromboxane A2