Different effects of dibutyryl cAMP on monolayer permeability in human aortic and coronary arterial endothelial cells

Abstract

Recent studies have demonstrated species- and/or organ-specific differences in the effects of dibutyryl cAMP (DBcAMP) on vascular permeability. In this study, we investigated the permeability of monolayers of human coronary arterial endothelial cells (HCAECs) and human aortic endothelial cells (HAECs) in the presence of DBcAMP using monolayer permeability models of endothelial cells and a double incubation chamber for measurement of FITC-labeled albumin or FITC-dextran (4 kDa) transfer through the monolayer. DBcAMP significantly lowered monolayer permeability in the HCAECs but had no effect in the HAECs when compared with untreated cells (P < 0.01). A cAMP-dependent protein kinase (PKA) inhibitor, Rp-8-Br-cAMPS (10-5 M), significantly reversed the DBcAMP induced decease in permeability of the HCAEC monolayer to the level of untreated cells. Rp-8-Br-cAMPS (10-5 M) and Sp-cAMPS (a PKA activator) had nosignificant effect on the permeability of the HAEC monolayer after treatment with DBcAMP. These results indicate that DBcAMP diminishes the permeability of an HCAEC monolayer via a cAMP-mediated PKA pathway but does not do so in HAECs, suggesting that the effects of cAMP on permeability of endothelial cell monolayers are dependent on the origin of the cells. Key words: Dibutyryl cAMP, endothelial cells, permeability.