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dc.contributor.authorKopperud, Reidun Kristinen_US
dc.contributor.authorRygh, Cecilie Brekkeen_US
dc.contributor.authorKarlsen, Tine Veronicaen_US
dc.contributor.authorKrakstad, Camillaen_US
dc.contributor.authorKleppe, Runeen_US
dc.contributor.authorHøivik, Erling Andreen_US
dc.contributor.authorBakke, Mariten_US
dc.contributor.authorTenstad, Olaven_US
dc.contributor.authorSelheim, Frodeen_US
dc.contributor.authorLiden, Åsaen_US
dc.contributor.authorMadsen, Liseen_US
dc.contributor.authorPavlin, Tinaen_US
dc.contributor.authorTaxt, Torfinnen_US
dc.contributor.authorKristiansen, K.en_US
dc.contributor.authorCurry, FEen_US
dc.contributor.authorReed, Rolf K.en_US
dc.contributor.authorDoskeland, Stein Oveen_US
dc.PublishedKopperud R, Rygh CB, Karlsen TV, Krakstad C, Kleppe R, Høivik EA, Bakke M, Tenstad O, Selheim F, Liden Å, Madsen L, Pavlin T, Taxt T, kristiansen, Curry F, Reed RK, Doskeland SO. Increased microvascular permeability in mice lacking Epac1 (Rapgef3). Acta Physiologica. 2017;219(2):441–452eng
dc.description.abstractAim: Maintenance of the blood and extracellular volume requires tight control of endothelial macromolecule permeability, which is regulated by cAMP signalling. This study probes the role of the cAMP mediators rap guanine nucleotide exchange factor 3 and 4 (Epac1 and Epac2) for in vivo control of microvascular macromolecule permeability under basal conditions. Methods: Epac1 / and Epac2 / C57BL/6J mice were produced and compared with wild-type mice for transvascular flux of radio-labelled albumin in skin, adipose tissue, intestine, heart and skeletal muscle. The transvascular leakage was also studied by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using the MRI contrast agent Gadomer-17 as probe. Results: Epac1 / mice had constitutively increased transvascular macromolecule transport, indicating Epac1-dependent restriction of baseline permeability. In addition, Epac1 / mice showed little or no enhancement of vascular permeability in response to atrial natriuretic peptide (ANP), whether probed with labelled albumin or Gadomer-17. Epac2 / and wild-type mice had similar basal and ANP-stimulated clearances. Ultrastructure analysis revealed that Epac1 / microvascular interendothelial junctions had constitutively less junctional complex. Conclusion: Epac1 exerts a tonic inhibition of in vivo basal microvascular permeability. The loss of this tonic action increases baseline permeability, presumably by reducing the interendothelial permeability resistance. Part of the action of ANP to increase permeability in wild-type microvessels may involve inhibition of the basal Epac1-dependent activity.en_US
dc.rightsAttribution CC BY-NC-NDeng
dc.subjectatrial natriuretic peptideeng
dc.subjectendothelial junctioneng
dc.subjectEpac deletion (mouse)eng
dc.subjectmicrovascular permeability (in vivo)eng
dc.titleIncreased microvascular permeability in mice lacking Epac1 (Rapgef3)en_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2016 The Author(s)
dc.source.journalActa Physiologica

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