Micro- and macrovascular endothelial cells in beta-adrenergic regulation of transendothelial permeability.
Barrier function of endothelial cells (EC) was modulated using beta-adrenergic 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 confluency, transendothelial exchange of the diffusion marker fluorescein isothiocyanate-dextran was determined. Microvascular retinal EC monolayers are half as permeable as monolayers from macrovascular BAEC. When EC are stimulated with beta-adrenergic receptor (AR) agonists, monolayer permeability decreases, and the amount of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) increases in both cell types. Comparison of the half-maximum concentrations causing change in permeability (pEC50) shows direct coupling between beta-AR and adenylate cyclase. The beta 2-selective agonist FOR stimulates cAMP synthesis in BAEC with a pEC50 value of 9.37 and decreases permeability with a pEC50 value of 9.72. In BREC, the pEC50 values of ISO concerning stimulation of cAMP synthesis and the decrease of permeability are also very similar, 5.32 and 5.34, respectively. BREC are not as sensitive to beta 2-AR agonists as BAEC. The pEC50 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-selective AR agonist in BREC and BAEC.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D011493:Protein Kinase C / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012171:Retinal Vessels / Q000166:cytology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases