title: PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40206, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Clavijo
authors.forename: M B
authors.initials: MB
authors.lastname: Carter
authors.forename: P J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: W B
authors.initials: WB
authors.lastname: Wead
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010972:Platelet Activating Factor