Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, Würzburg, Germany.
Microcirculation. 2011 Feb;18(2):118-27. doi: 10.1111/j.1549-8719.2010.00072.x.
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.
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.
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.
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.
已知内皮细胞内的 cAMP 信号可降低细胞旁通透性，并在各种病理条件下保护屏障功能丧失。由于β-肾上腺素能受体的激活会增加细胞内 cAMP，因此我们测试了β-肾上腺素能受体信号是否有助于维持内皮屏障的基础特性。
我们比较了体内大鼠后微静脉的水力传导率与体外微血管内皮细胞中 β-肾上腺素能受体介导的 cAMP 水平变化后的电阻测量值和内皮细胞黏附连接的重排。
β-肾上腺素能受体抑制剂普萘洛尔增加了水力传导率，降低了微血管内皮细胞单层的 cAMP 水平和 TER，并诱导了 VE-钙粘蛋白染色的片段化。相比之下，肾上腺素的激活既增加了 cAMP 水平和 TER，又导致 VE-钙粘蛋白分布的线性化，但这不足以阻止普萘洛尔引起的屏障破坏。同样，PDE 抑制并不能阻止普萘洛尔诱导的 TER 降低和 VE-钙粘蛋白重排，而 AC 激活增加 cAMP 的形成则增强了内皮屏障在基础条件下和普萘洛尔处理条件下的功能。
我们的结果表明，β-肾上腺素能受体信号激活介导的 cAMP 的产生有助于维持基础条件下的内皮屏障特性。
