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

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 additon 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 generated by ANP and SNP or addition of 8-bromo-cGMP significantly suppressed the increase in permeability. Inhibition of nitric oxide production with 10-4 M N(G)-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.
Chemicals/CAS: 8 bromo cyclic GMP, 31356-94-2; atrial natriuretic factor, 85637-73-6; cyclic GMP, 7665-99-8; forskolin, 66575-29-9; n(g) nitroarginine methyl ester, 50903-99-6; nitroprusside sodium, 14402-89-2, 15078-28-1; thrombin, 9002-04-4; 8-Bromo Cyclic Adenosine Monophosphate, 23583-48-4; Adenylate Cyclase, EC 4.6.1.1; Arginine, 74-79-3; Atrial Natriuretic Factor, 85637-73-6; Cyclic AMP, 60-92-4; Cyclic GMP, 7665-99-8; Forskolin, 66428-89-5; Guanylate Cyclase, EC 4.6.1.2; NG-Nitroarginine Methyl Ester, 50903-99-6; Nitric Oxide, 10102-43-9; Nitroprusside, 15078-28-1; Thrombin, EC 3.4.21.5