Hyperosmolar Solution Inhibits The Contraction Of Airway Smooth Muscle Induced By Ca²⁺ Sensitization

Previous studies have indicated that hyperosmolar solutions(HS)can be used to relax the airway.However,the underlying mechanism is still unclear.The aim of this study was to clarify the mechanism underlying relaxation induced by HS in mouse airway.Acetylcholine(ACH)pre-contracted mouse tracheal rings,which were relaxed by high concentration of NaCl in a dose-dependent manner.Based on the damage and the diastolic level induced by HS,we defined that 5% NaCl solution will be utilized in the following experiments,which can relax control and asthmatic trachea and human bronchus.Removing of the tracheal epithelium,HS still induced relaxation,thus,the intact tracheal rings were used in the following experiments.To define the relationship between HS-induced relaxation and the intracellular Ca2+ in mouse ASMCs,we measured Ca2+ in ASMCs.It increased,not decreased,following the treat of HS.This result suggests that HS-induced relaxation will not relate to the Ca2+ levels,probably to the Ca2+ sensitization.In the presence of 10 ?M Y-27632,an inhibitor of RhoA that is one step of Ca2+ sensitization pathway,HS-induced relaxation reduced.This means the RhoA mediates HS-evoked relaxation.Using Western blotting to measure the phosphorylation of myosin light chain LC20 was determined that HS resulted in LC20 phosphorylation decrease.In a word,the results indicate that HS decreases Ca2+ sensitization,resulting in airway relaxation.