Contrasting effects of hypochlorous acid and hydrogen peroxide on endothelial permeability: Prevention with cAMP drugs

L. Ochoa, G. Waypa, Jr Mahoney J.R., L. Rodriguez, F. L. Minnear

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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 (125l-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 in-creased permeability induced by either oxidant,.

Original languageEnglish (US)
Pages (from-to)1247-1255
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume156
Issue number4 PART I
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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