Leukotrienes are a newly discovered family of biologically active compounds. They constrict bronchioles and arterioles, dilate venules, cause plasma exudation and chemotaxis. They may be responsible, at least in part, for some of the cardiovascular effects of anaphylaxis. We propose to study the release of leukotrienes in certain models of anaphylaxis and their role in the cardiovascular manifestations of this reaction. We plan to investigate two models of anaphylaxis: a) the mesenteric bed of the sensitized rat, and b) the heart of sensitized rabbit and rat. The vascular bed studies will involve microscopic observation of the changes in vascular caliber, plasma exudation and margination and diapedesis of leukocytes. We will investigate the specific leukotrienes involved and which leukocytes contribute to their production. The IgE-mediated anaphylactic reaction will be compared with reactions requiring complement. The possibility of mast cell-macrophage interaction will be tested in vitro. In the rabbit, cardiac effects will be studied in the intact animal by monitoring systemic blood pressure, right ventricular pressure and electrocardiogram. In the ex vivo perfused rat heart coronary vascular resistance and contractibility will be followed. The involvement of leukotrienes and their interaction with other humoral substances will be determined by the use of specific inhibitors for leukotrienes, histamine, prostaglandins and other agents. The data obtained should bring about a greater understanding of cardiovascular alterations taking place during anaphylaxis and other intermediate hypersensitivity reactions.
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