Transient receptor potential vanilloid 4 channels mediate resistive breathing-induced acute lung injury

Abstract

Introduction: Resistive breathing (RB) is the hallmark of the pathophysiology of obstructive airway diseases. RB is associated with increased mechanical stress on the lung and induces lung injury in previously healthy animals.TRPV4 are mechanosensitive channels, implicated recently in the pathogenesis of lung injury. Aim: To investigate the role of TRPV4 channels in RB-induced lung injury. Methods: Spontaneously breathing C57BL/6 mice were subjected to RB by tracheal banding. Anaesthetized mice were placed under a surgical microscope and the surface area of the trachea was reduced to half by placement of a nylon band around the trachea. TRPV4 antagonist, HC-067047 (10 mg/kg ip), was administered either prior to RB and at 12 hrs following initiation of RB (preventive) or only at 12 hrs after the initiation of RB (therapeutic strategy). Following 24 hrs of RB in total, a static pressure-volume curve was obtained. Total protein, KC and IL-6 levels were measured in BAL fluid. Surfactant Protein (Sp)D in plasma was measured and a lung injury score was estimated by histology. Results: RB decreased static compliance (Cst) (p=0.016), increased total protein in BAL (p Conclusion: TRPV4 inhibition protects against RB-induced lung injury.