Beta-Adrenergic Stimulation Contributes to Maintenance of Endothelial Barrier Functions Under Baseline Conditions

P>Objectives: 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 beta-adrenergic receptors elevates cellular cAMP, we tested whether beta-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 beta-adrenergic receptor-mediated changes of cAMP levels. Results: Inhibition of beta-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 beta-adrenergic receptor signaling contributes to the maintenance of endothelial barrier properties under baseline conditions.