Am. J. Respir. Crit. Care Med., Volume 156, Number 4, October 1997, 1247-1255

Contrasting Effects of Hypochlorous Acid and Hydrogen Peroxide on Endothelial Permeability
Prevention with cAMP Drugs

LUIS OCHOA, GREGORY WAYPA, JOHN R. MAHONEY Jr., LUIS RODRIGUEZ, and FRED L. MINNEAR

Departments of Physiology and Cell Biology, Pediatrics, and Experimental and Molecular Pathology, Albany Medical College, Albany, New York

Activated polymorphonuclear leukocytes generate a cascade of reduced oxygen metabolites. In addition to their antimicrobial role, hydrogen peroxide (H₂O₂) and hypochlorous acid (HOCl) function as inflammatory mediators and increase the protein permeability of the vascular endothelium. The objectives of the present study were to compare the effects of H₂O₂ and HOCl with respect to relative potencies and the time course and magnitude of changes in cell shape and permeability of endothelial cell monolayers derived from bovine pulmonary artery, to determine if HOCl produced by conversion of H₂O₂ with myeloperoxidase and Cl produces comparable results as the direct administration of HOCl, and to show that adenosine 3',5'-cyclic monophosphate (cAMP)-enhancing agents can prevent the increased endothelial permeability induced by HOCl and H₂O₂. HOCl given directly or produced by myeloperoxidase, H₂O₂, and Cl caused faster and greater changes in cell shape (cell retraction), electrical resistance, and protein permeability (¹²⁵I-labeled albumin clearance) of endothelial cell monolayers than induced by H₂O₂. HOCl (10 to 100 µM) induced these changes within 1 to 3 min, whereas H₂O₂ (50 to 400 µM) required ~ 30 min. 8-Bromo-cAMP prevented the increased endothelial protein permeability induced by HOCl or H₂O₂, but isoproterenol only prevented the H₂O₂ response. Thus, HOCl at a much lower concentration caused a faster and greater increase in endothelial permeability in vitro than H₂O₂, and an increased intracellular level of cAMP prevented the increased permeability induced by either oxidant.

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