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

J Vasc Res. Jan-Feb 1994;31(1):42-51. doi: 10.1159/000159030.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenylyl Cyclases / metabolism
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Atrial Natriuretic Factor / pharmacology
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic GMP / physiology*
  • Electric Conductivity
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Guanylate Cyclase / metabolism
  • Humans
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / pharmacology
  • Nitroprusside / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology
  • Thrombin / pharmacology
  • Umbilical Arteries / drug effects
  • Umbilical Arteries / physiology

Substances

  • Nitroprusside
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Arginine
  • Cyclic AMP
  • Thrombin
  • Adenylyl Cyclases
  • Guanylate Cyclase
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester