title: Beta-adrenergic stimulation contributes to maintenance of endothelial barrier functions under baseline conditions.
abstract: OBJECTIVE
  cAMP signaling within the endothelium is known to reduce paracellular permeability and to protect against loss of barrier functions under various pathological conditions. Because activation of β-adrenergic receptors elevates cellular cAMP, we tested whether β-adrenergic receptor signaling contributes to the maintenance of baseline endothelial barrier properties.
  
  
  METHODS
  We compared hydraulic conductivity of rat postcapillary venules in vivo with resistance measurements and with reorganization of endothelial adherens junctions in cultured microvascular endothelial cells downstream of β-adrenergic receptor-mediated changes of cAMP levels.
  
  
  RESULTS
  Inhibition of β-adrenergic receptors by propranolol increased hydraulic conductivity, reduced both cAMP levels and TER of microvascular endothelial cell monolayers and induced fragmentation of VE-cadherin staining. In contrast, activation by epinephrine both increased cAMP levels and TER and resulted in linearized VE-cadherin distribution, however this was not sufficient to block barrier-destabilization by propranolol. Similarly, PDE inhibition did not prevent propranolol-induced TER reduction and VE-cadherin reorganization whereas increased cAMP formation by AC activation enhanced endothelial barrier functions under baseline conditions and under conditions of propranolol treatment.
  
  
  CONCLUSIONS
  Our results indicate that generation of cAMP mediated by activation of β-adrenergic receptor signaling contributes to the maintenance of endothelial barrier properties under baseline conditions.
authors.affiliation: Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, Würzburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Spindler
authors.forename: Jens
authors.initials: J
authors.lastname: Waschke
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction; D014699:Venules / Q000187:drug effects / Q000502:physiology; D000099152:Cadherin 5
chemical_list: D000262:Adenylyl Cyclases; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015703:Antigens, CD; D015820:Cadherins; D000242:Cyclic AMP; D004837:Epinephrine; D058988:Phosphodiesterase 4 Inhibitors; D011433:Propranolol; D011943:Receptors, Adrenergic, beta; D020889:Rolipram; D000099152:Cadherin 5