Platelet-Activating Factor-Induced Cellular And Pathophysiological Responses In The Cardiovascular-System

Recent findings in several laboratories have demonstrated the important interactions of platelet-activating factor (PAF) with vascular endothelial cells, and thus the potential role of this lipid mediator in the pathophysiology of the cardiovascular system. PAF potently and specifically stimulates the in situ and in vivo release of tissue-type plasminogen activator from the vascular endothelium [Emeis and Kluft, 1985]. Several lines of evidence indicate that PAF may play a critical role in the neutrophil adhesion to endothelial cells stimulated with thrombin or leukotrienes [Zimmerman et al., 1985]. PAF is a potent stimulator of Ca+2 efflux from endothelial cells, which thus might be an early step in the suspected involvement of the endothelium in in vivo responses to PAF, such as hypotension and increased vascular permeability [Brock and Gimbrone, 1986]. In our own laboratory, we have developed a specific and potent PAF receptor antagonist, L-652,731, in order to determine the role of PAF in different animal models of disease. Utilizing this receptor antagonist as well as other criteria, PAF is indicated to be a major mediator of the endotoxin-induced hypotension in rats and soluble immune complex-induced hypotension and extravasation, also in rats. The immune complex-induced increased plasma glucosaminidase is partially mediated by PAF, whereas the immediate and complete neutropenia is not indicated to involve PAF.