Journal of Applied Physiology AJP: Heart and Circulatory Physiology
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J Appl Physiol 90: 261-268, 2001;
8750-7587/01 $5.00
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Vol. 90, Issue 1, 261-268, January 2001

PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat

Leonardo C. Clavijo1, Mary B. Carter2, Paul J. Matheson3, Mark A. Wilson1,2,3,4, William B. Wead1,3, and R. Neal Garrison1,2,3,4

Departments of 1 Physiology and Biophysics and 2 Surgery and 3 Center for Excellence in Applied Microcirculatory Research, University of Louisville, and 4 Louisville Veterans Affairs Medical Center, Louisville, Kentucky 40206

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.

platelet-activating factor; septic shock; gram negative; lung injury; pulmonary edema; videomicroscopy; pulmonary arterial catheterization


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