Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases

  • James Surapisitchat
  • Joseph A. BeavoEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 204)


The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction.


cAMP cGMP Endothelial barrier Endothelial permeability Phosphodiesterase 



The authors would like to thank the members of the Beavo lab for their support over the course of these experiments. This work was funded by grants GM083926, AR056221, and Foundation Leducq to J.A.B.


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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Washington School of MedicineSeattleUSA
  2. 2.McEwen Centre for Regenerative MedicineUniversity Health NetworkTorontoCanada

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