15‐hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice

Abstract

Allergic rhinitis (AR) is one of the most common allergic inflammatory diseases worldwide. In AR, increased blood flow and vascular permeability in nasal mucosa cause rhinorrhea and nasal congestion. We investigated the role of an 11Z,14Z‐eicosadienoic acid‐derived metabolite, 15‐hydroxy‐11Z,13Z‐eicosadienoic acid (15‐HEDE), in functional changes in vasculature and nasal congestion in AR. Repeated intranasal administration of Ovalbumin (OVA) caused AR symptoms, such as sneezing and nasal congestion, in mice. OVA administration increased the level of 15‐HEDE in nasal lavage fluid, which reached approximately 0.6 ng/ml after ten OVA treatments. Upon measuring vascular contraction, treatment with 0.1–3 μM 15‐HEDE did not cause contraction in mouse aortae, while it dilated aortae that were pre‐contracted by thromboxane receptor stimulation. Pretreatment with the voltage‐gated K+ (KV) channel inhibitor 4‐aminopyridine significantly inhibited the 15‐HEDE‐induced vascular relaxation. Intravital imaging showed that administration of 1 μg 15‐HEDE dilated blood vessels, and Mile's assay demonstrated that this administration also caused dye leakage, indicating vascular hyperpermeability in mouse ears. Computed tomography scanning and morphological study revealed that administration of 3 μg 15‐HEDE narrowed nasal passages and thickened nasal mucosa in mice. Finally, we confirmed that treating mice with 3 μg 15‐HEDE caused rhinitis symptoms, such as abdominal breathing, and reduced respiratory frequency, suggesting nasal congestion. 15‐HEDE caused vasodilation by activating KV channels and increased vascular permeability, which may lead to nasal congestion. Furthermore, 15‐HEDE might be a new lipid mediator that exacerbates nasal congestion in AR.