Previous studies in our laboratory showed that ANP inhibits increases in 
endothelial monolayer permeability to macromolecules induced by thrombin. In 
this present study, we investigated the second messenger system involved in the 
influence of ANP on monolayer permeability. In bovine aortic endothelial cells 
(BAEC), ANP (100 nM) caused increased cGMP levels which were measurable at 30 
sec and maximal at 3 min. Addition of 8-bromo cGMP (1 mM) to BAEC monolayers 
mimicked the actions of ANP by inhibiting thrombin- mediated increases in 
permeability to [125I]-labeled bovine serum albumin. Inhibition of increases in 
permeability by lower concentrations of ANP was enhanced by the cGMP-selective 
phosphodiesterase inhibitor, M&B 22948 (100 microM). The use of ANP structural 
analogs which stimulate cGMP production (AP III or BNP) prevented 
thrombin-induced increases in monolayer permeability, whereas AP-I, which does 
not increase cGMP levels, was ineffective.