Benzbromarone (Benzb) treatment decreases the EC₅₀ dose of isoproterenol (iso) or albuterol required for relaxation. (A) When guinea pig tracheal rings were contracted with acetylcholine (Ach) EC₅₀ and then treated with cumulatively increasing concentrations of isoproterenol, a dose-dependent relaxation was observed. At the 0.5 nM concentration of isoproterenol, vehicle (0.1% dimethyl sulfoxide [DMSO]), 10 μM Benzb, or 25 μM Benzb was added. The EC₅₀ for relaxation with vehicle-treated guinea pig tracheal rings was 5.5 nM isoproterenol. Benzb 10 μM treatment decreased the isoproterenol EC₅₀ for relaxation from 5.5 to 2.1 nM (n = 9, P < 0.01). Benzb 25 μM treatment decreased the isoproterenol EC₅₀ for relaxation from 5.5 to 0.7 nM (n = 9 rings from four animals, P < 0.01 two-way ANOVA). (B) Treatment with a combination of isoproterenol 1 nM and Benzb 10 μM (n = 12) shows a significant decrease in airway smooth muscle force compared with treatments with either compound alone (relaxation not normalized to DMSO vehicle control, isoproterenol study carried out in the presence of DMSO vehicle of Benzb). *P < 0.05 compared with vehicle, $P < 0.001 compared with isoproterenol 1 nM alone (n = 10), and #P < 0.05 compared with Benzb 10 μM alone (n = 9). ns = not significant. (C) When human airway smooth muscle was contracted with Ach EC₅₀ and then treated with cumulatively increasing concentrations of albuterol, a dose-dependent relaxation was observed. At the 0.5 nM concentration of albuterol, vehicle (0.1% DMSO) or 25 μM Benzb was added. The EC₅₀ for relaxation with vehicle was 62.9 nM albuterol. Benzb 25 μM treatment decreased the albuterol EC₅₀ for relaxation from 62.9 to 23.2 nM (P < 0.05 two-way ANOVA, n = 5 samples from three patients).