Griffin, M. Pamela. Role for anions in pulmonary endothelial permeability. J. Appl. Physiol. 83(2): 615-622, 1997.-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that are mediated by Cl flux. We tested the hypothesis that anion-mediated changes in endothelial cells result in changes in endothelial permeability. We measured permeation of radiolabeled albumin across bovine pulmonary arterial endothelial monolayers when the extracellular anion was Cl, Br, I, F, acetate (Ac), gluconate (G), and propionate (Pr). Permeability to albumin (P_albumin) was calculated before and after addition of 0.2 mM of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), which reduces permeability. In Cl, the P_albumin was 3.05 ± 0.86 × 10⁶ cm/s and fell by 70% with the addition of IBMX. The initial P_albumin was lowest for Pr and Ac. Initial P_albumin was higher in Br, I, G, and F than in Cl. A permeability ratio was calculated to examine the IBMX effect. The greatest IBMX effect was seen when Cl was the extracellular anion, and the order 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 endothelial permeability in this system. When Cl was the extracellular anion, varying [Ca²⁺]_o from 0.2 to 2.8 mM caused a change in initial P_albumin but no change in the IBMX effect. The anion channel blockers 4-acetamido-4-isothiocyanotostilbene-2,2-disulfonic acid (0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initial P_albumin and the IBMX effect. The anion transport blockers bumetanide (0.2 mM) and furosemide (1 mM) had no such effects. We conclude that extracellular anions influence bovine pulmonary arterial endothelial permeability and that the pharmacological profile fits better with the activity of anion channels than with other anion transport processes.