MICROVASCULAR AND MACROVASCULAR ENDOTHELIAL-CELLS IN BETA-ADRENERGIC REGULATION OF TRANSENDOTHELIAL PERMEABILITY

Barrier function of endothelial cells (EC) was modulated using beta-ad renergic agonists, e.g., isoproterenol (ISO) and formoterol (FOR). To get a direct comparison between EC from different vascular sources, we isolated EC from aorta (BAEC) and retina (BREC) of the same calf. For permeability studies, EC were cultured on polycarbonate filters. At c onfluency, transendothelial exchange of the diffusion marker fluoresce in isothiocyanate-dextran was determined. Microvascular retinal EC mon olayers are half as permeable as monolayers from macrovascular BAEC. W hen EC are stimulated with beta-adrenergic receptor (AR) agonists, mon olayer permeability decreases, and the amount of intracellular adenosi ne 3',5'-cyclic monophosphate (cAMP) increases in both cell types. Com parison of the half-maximum concentrations causing change in permeabil ity (pEC(50)) shows direct coupling between beta-AR and adenylate cycl ase. The beta(2)-selective agonist FOR stimulates cAMP synthesis in BA EC with a PEC(50) value of 9.37 and decreases permeability with a PEC( 50) value of 9.72. In BREC, the PEC(50) values of ISO concerning stimu lation of cAMP synthesis and the decrease of permeability are also ver y similar, 5.32 and 5.34, respectively. BREC are not as sensitive to b eta(2)-AR agonists as BAEC. The PEC(50) value of FOR influence on BREC permeability is 8.77 in comparison with 9.72 for BAEC. These results could be interpreted with different affinities of the beta(2)-selectiv e AR agonist in BREC and BAEC.