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 journalArticle

15 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 1 2000


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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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    Waypa, G. B., Morton, C. A., Vincent, P. A., Mahoney, J. R., Johnston, W. K., & Minnear, F. L. (2000). Oxidant-increased endothelial permeability: Prevention with phosphodiesterase inhibition vs. cAMP production. Journal of Applied Physiology, 88(3), 835-842.