Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle

Diclofenac sodium (DCF) is a nonsteroidal anti-inflammatory drug (NSAID) and is widely used as an analgesic and anti-inflammatory agent. Herein, we found that DCF could relax high K⁺ (80 mM K⁺)-/ACh-precontracted tracheal rings (TRs) in mice. This study aimed to elucidate the underlying mechanisms of DCF-induced relaxations. The effects of DCF on airway smooth muscle (ASM) cells were explored using multiple biophysiological techniques, such as isometric tension measurement and patch-clamping experiments. Both high K⁺- and ACh-evoked contraction of TRs in mice were relaxed by DCF in a dose-dependent manner. The results of isometric tension and patch-clamping experiments demonstrated that DCF-induced relaxation in ASM cells was mediated by cytosolic free Ca²⁺, which was decreased via inhibition of voltage-dependent L-type Ca²⁺ channels (VDLCCs), nonselective cation channels (NSCCs), and Na^+/Ca²⁺ exchange. Meanwhile, DCF also enhanced large conductance Ca²⁺ activated K⁺ (BK) channels, which led to the relaxation of ASMs. Our data demonstrated that DCF relaxed ASMs by decreasing the intracellular Ca²⁺ concentration via inhibition of Ca²⁺ influx and Na⁺/Ca²⁺ exchange. Meanwhile, the enhanced BK channels also played a role in DCF-induced relaxation in ASMs. These results suggest that DCF is a potential candidate for antibronchospasmic drugs used in treating respiratory diseases such as asthma and chronic obstructive pulmonary disease.