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PubMed · 7903872

Cyclic-GMP-mediated decrease in permeability of human umbilical and pulmonary artery endothelial cell monolayers.

R G Westendorp·R Draijer·A E Meinders·V W van Hinsbergh
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Abstract

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(-7) M atrial natriuretic peptide (ANP) or 10(-4) 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(-4) M NG-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 transendothelial 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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8-Bromo Cyclic Adenosine MonophosphateAdenylyl CyclasesArginineAtrial Natriuretic FactorCapillary PermeabilityCells, CulturedColforsinCyclic AMPCyclic GMPElectric ConductivityEndothelium, VascularGuanylate CyclaseHumansNG-Nitroarginine Methyl EsterNitric OxideNitroprussidePulmonary ArteryThrombinUmbilical ArteriesJournal ArticleResearch Support, Non-U.S. Gov't

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R G Westendorp, R Draijer, A E Meinders, V W van Hinsbergh. Cyclic-GMP-mediated decrease in permeability of human umbilical and pulmonary artery endothelial cell monolayers.. https://doi.org/10.1159/000159030

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