Permeability of endothelial monolayers to albumin is increased by bradykinin and inhibited by prostaglandins

Using monolayers of bovine aortic endothelial cells (BAEC) in modified Boyd en chambers, we examined the role of prostaglandins (PGs) in the bradykinin (BK)-induced increase of albumin permeability. BK induced a concentration- dependent increase of the permeability of BAEC, which reached 49.9 +/- 1% a t the concentration of 10(-8) M. Two inhibitors of the prostaglandin G/H sy nthase, indomethacin (2.88 muM) and ibuprofen (10 muM), potentiated BK-indu ced permeability 1.8- and 3.9-fold, respectively. Exogenously administered PGE(2) and iloprost, a stable analog of prostacyclin, attenuated the effect of BK in a concentration-dependent manner. Butaprost equally reduced the e ffect of BK, suggesting the participation of the EP2 receptor in this pheno menon. However, the EP4-selective antagonist AH-23848 did not significantly inhibit the protective effect of PGE(2). The inhibitory effect of PGE2 was reversed by the adenylate cyclase inhibitor MDL-12330A (10 muM). These res ults suggest that BK-induced increase of permeability of BAEC monolayer to I-125-labeled albumin is negatively regulated by PGs. This postulated autoc rine activity of PGs may involve an increase in the intracellular level of cAMP.