Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue

Abstract

Recurrent airway obstruction (RAO) is a main characteristic of horses with severe equine asthma syndrome. The presence of bacterial lipopolysaccharide (LPS) in the airways of horses is thought to play a crucial role in the clinical expression of this disorder. This study pharmacologically characterized the effect of LPS on the responsiveness of equine bronchial tissue. Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml) and then stimulated by electrical field stimulation (EFS). The role of capsaicin sensitive-sensory nerves (capsaicin desensitization treatment), neurokinin-2 (NK₂) receptors (blocked by GR159897), transient receptor potential vanilloid type 1 receptors (TRPV1; blocked by SB366791), and neurokinin A (NKA) were investigated. Untreated bronchi were used as control tissues. LPS (1 ng/ml) significantly increased the EFS-evoked contractility of equine bronchi compared with control tissues (+742 ± 123 mg; P < 0.001). At higher concentrations LPS induced desensitization to airways hyperresponsiveness (AHR; EC₅₀: 5.9 ± 2.6 ng/ml). Capsaicin desensitization and GR159897 significantly prevented AHR induced by LPS at EFS_1-50Hz (-197 ± 25%; P < 0.01). SB366791 inhibited AHR at very low EFS frequency (EFS_1Hz -193 ± 29%; P < 0.01 vs. LPS-treated bronchi). LPS (1 ng/ml) significantly (P < 0.01) increased 3.7 ± 0.7 fold the release of NKA compared with control bronchi. LPS induces biphasic dysfunctional bronchial contractility due to the stimulation of capsaicin sensitive-sensory nerves, increased release of NKA, and activation of NK₂ receptors, whereas TRPV1 receptors appear to play a marginal role in this response. The overnight challenge with low concentrations of LPS represents a suitable model to investigate pharmacological options that may be of value in the treatment of equine RAO.

Keywords: Airway smooth muscle; Airways hyperresponsiveness; Lipopolysaccharide; Neurokinin A; Recurrent airway obstruction; Severe equine asthma syndrome.