Oxidant-increased endothelial permeability: Prevention with phosphodiesterase inhibition vs. cAMP production

Gregory B. Waypa, Christine A. Morton, Peter A. Vincent, John R. Mahoney, William K. Johnston, Fred L. Minnear*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The present objective was to determine whether hydrogen peroxide (H2O2) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by 125I-labeled albumin clearance (125I-albumin flux/perfusate concentration of 125I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product (PS) and the reflection coefficient (σ), H2O2 decreased σ from a control value of 0.93 to 0.38, did not change PS, and increased lung weight. Posttreatment with isoproterenol, a β2-adrenergic-receptor agonist, reduced the H2O2-induced decrease in σ to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H2O2- induced decrease in σ to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H2O2 increased PS. Therefore, H2O2 increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H2O2-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalJournal of applied physiology
Issue number3
StatePublished - Mar 2000


  • Desferrioxamine
  • Iron chelator
  • Isoproterenol
  • Lung weight
  • Permeability-surface area product
  • Phosphodiesterase inhibitor
  • Reflection coefficient
  • Vascular pressure
  • Vascular resistance

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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