Differential phosphodiesterase activity contributes to restrictive endothelial barrier function during angiogenesis

Lisa M. DeFouw, David O. DeFouw

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Angiogenic endothelial hyperpermeability is abruptly diminished between days 4.5 and 5.0 of the 18-day lifespan of the chick chorioallantoic membrane. Here, we evaluated phosphodiesterase (PDE) activity during the differentiation of barrier function. At day 4.5, rolipram-mediated inhibition of cAMP-specific PDE IV reduced FITC-dextran extravasation. Moreover, inhibition of PDE III by HL 725, but not PDE I by 8-IBMX, decreased the temporal angiogenic endothelial hyperpermeability. Reduced FITC-dextran was also observed at day 4.5 after application of KT 5823, a selective inhibitor of cGMP-specific protein kinase G (PKG), LY 83583, an inhibitor of soluble guanylate cyclase, or LNMMA, an inhibitor of nitric oxide synthase. At day 5.0, Rp-cAMPS-mediated inhibition of cAMP-specific protein kinase A (PKA) diminished barrier function and interstitial accumulation of FITC-dextran was increased. In all cases, the mean widths of interendothelial separation remained uniform. Together, the results support the concept that differentiation of restrictive angiogenic endothelial barrier function in vivo includes inactivation of PDE III and PDE IV with consequent up-regulation of cAMP/PKA signaling and down-regulation of the cGMP/PKG pathway.

Original languageEnglish (US)
Pages (from-to)263-270
Number of pages8
JournalMicrovascular Research
Issue number3
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology


  • Angiogenic endothelium
  • Permeability
  • Phosphodiesterase
  • cAMP
  • cGMP


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