[Ethacrynic acid inhibits airway smooth muscle contraction in mice]

The aim of this study was to investigate the inhibitory effect and the underlying mechanism of ethacrynic acid (EA) on the contraction in mice. BL-420S force measuring system was used to measure the tension of mouse tracheal rings. The whole cell patch clamp technique was utilized to record the channel currents of airway smooth muscle (ASM) cells. The calcium imaging system was used to determine the intracellular CA²⁺ concentration ([CA²⁺]_i) in ASM cells. The results showed that EA significantly inhibited the high K⁺ (80 mmol/L) and acetylcholine (ACh, 100 µmol/L)-induced contraction of mouse tracheal rings in a dose-dependent manner. The maximal relaxation percentages were (97.02 ± 1.56)% and (85.21 ± 0.03)%, and the median effective concentrations were (40.28 ± 2.20) μmol/L and (56.22 ± 7.62) μmol/L, respectively. EA decreased the K⁺ and ACh-induced elevation of [CA²⁺]_i from 0.40 ± 0.04 to 0.16 ± 0.01 and from 0.50 ± 0.01 to 0.39 ± 0.01, respectively. In addition, EA inhibited L-type voltage-dependent Calcium Channel (LVDCC) and store-operated Calcium Channel (SOCC) currents in ASM cells, and CA²⁺ influx. Moreover, EA decreased the resistance of the respiratory system (Rrs) in vivo in mice. These results indicated that EA inhibits LVDCC and SOCC, which results in termination of CA²⁺ influx and decreases of [CA²⁺]_i, leading to relaxation of ASM. Taken together, EA might be a potential bronchodilator.