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      Cyclic-GMP-Mediated Decrease in Permeability of Human Umbilical and Pulmonary Artery Endothelial Cell Monolayers


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          Endothelial cell contraction plays a pivotal role in the increased extravasation of fluid and macromolecules in vascular leakage. Previous studies have indicated that elevation of the adenosine 3’,5’-cyclic monophosphate (cAMP) concentration can improve the endothelial barrier function. In analogy with smooth muscle cell contraction, which is inhibited by both cAMP and guanosine 3’,5’-cyclic monophosphate (cGMP), we have compared the role of cAMP and cGMP in the regulation of the permeability of human endothelial cell monolayers. The cellular cGMP concentration was elevated 3- to 5-fold after addition of 10<sup>–7</sup> M atrial natriuretic peptide (ANP) or 10<sup>-4</sup> M sodium nitroprusside (SNP), both under basal and thrombin-stimulated conditions. After exposure to thrombin, cGMP generation by ANP or SNP or addition of 8-bromo-cGMP significantly suppressed the increase in permeability. Inhibition of nitric oxide production with 10<sup>–4</sup> M N<sup>G</sup>-nitro-L-arginine methyl ester increased the permeability of endothelial monolayers in the majority of the tested cultures, an effect that could be counteracted by addition of 8-bromo-cGMP or ANP. An increase of cAMP upon the addition of forskolin reduced the permeability in all endothelial cell strains under basal conditions and after exposure to thrombin. The forskolin- and 8-bromo-cGMP-mediated decreases in permeability were accompanied by increases in transendothehal electrical resistance. These in vitro data indicate that, in addition to cAMP, cGMP can act as a potent fine-regulator of endothelial permeability.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          23 September 2008
          : 31
          : 1
          : 42-51
          aGaubius Laboratory, IWO-TNO, and bDepartment of General Internal Medicine, University Hospital Leiden, Leiden, The Netherlands
          159030 J Vasc Res 1994;31:42–51
          © 1994 S. Karger AG, Basel

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          Pages: 10
          Research Paper


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