ROLE FOR ANIONS IN PULMONARY ENDOTHELIAL PERMEABILITY

beta-Adrenergic stimulation reduces albumin permeation across pulmonar y artery endothelial monolayers and induces changes in cell morphology that are mediated by Cl- flux. We tested the hypothesis that anion-me diated changes in endothelial cells result in changes in endothelial p ermeability. We measured permeation of radiolabeled albumin across bov ine pulmonary arterial endothelial monolayers when the extracellular a nion was Cl-, Br-, I-, F-, acetate (Ac-), gluconate (G(-)), and propio nate (Pr-). Permeability to albumin (P-albumin) was calculated before and after addition of 0.2 mM of the phosphodiesterase inhibitor 3-isob utyl-1-methylxanthine (IBMX), which reduces permeability. In Cl-, the P-albumin was 3.05 +/- 0.86 x 10(-6) cm/s and fell by 70% with the add ition of IBMX. The initial P-albumin was lowest for Pr- and Ac-. Initi al P-albumin was higher in Br-, I-, G(-), and F- than in Cl-. A permea bility ratio was calculated to examine the IBMX, effect. The greatest IBMX effect was seen when Cl- was the extracellular anion, and the ord er among halide anions was Cl- > Br- > I- > F-. Although the level of extracellular Ca2+ concentration ([Ca2+](o)) varied over a wide range in the anion solutions, [Ca2+](o) did not systematically affect endoth elial permeability in this system. When Cl- was the extracellular anio n, varying [Ca2+](o) from 0.2 to 2.8 mM caused a change in initial P-a lbumin but no change in the IBMX effect. The anion channel blockers ac etamido-4'-isothiocyanotostilbene-2,2-disulfonic acid (0.25 mM) and an thracene-9-carboxylic acid (0.5 mM significantly altered initial P-alb umin and the IBMX effect. The anion transport blockers bumetanide (0.2 mM) and furosemide (1 mM) had no such effects. We conclude that extra cellular anions influence bovine pulmonary arterial endothelial permea bility and that the pharmacological profile fits better with the activ ity of anion channels than with other anion transport processes.