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⁺ (K_V) 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 K_V 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.

中文翻译：

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15-羟基二十碳二烯酸是小鼠鼻塞的加重因素

过敏性鼻炎（AR）是世界范围内最常见的过敏性炎症疾病之一。在 AR 中，鼻黏膜血流量和血管通透性增加会导致流鼻涕和鼻塞。我们研究了 11Z,14Z-二十碳二烯酸衍生代谢物 15-羟基-11Z,13Z-二十碳二烯酸 (15-HEDE) 在 AR 血管系统功能变化和鼻塞中的作用。重复鼻内给予卵清蛋白 (OVA) 会导致小鼠出现 AR 症状，例如打喷嚏和鼻塞。OVA 给药增加了鼻腔灌洗液中 15-HEDE 的水平，在十次 OVA 治疗后达到约 0.6 ng/ml。在测量血管收缩时，用 0.1–3 μM 15-HEDE 处理不会引起小鼠主动脉收缩，但会扩张因血栓素受体刺激而预收缩的主动脉。⁺ (K _V ) 通道抑制剂 4-氨基吡啶显着抑制 15-HEDE 诱导的血管舒张。活体成像显示，施用 1 μg 15-HEDE 可扩张血管，Mile 的测定表明，这种施用也会导致染料渗漏，表明小鼠耳朵的血管通透性过高。计算机断层扫描和形态学研究表明，给予 3 μg 15-HEDE 可缩小小鼠的鼻道并增厚鼻粘膜。最后，我们证实用 3 μg 15-HEDE 治疗小鼠会引起鼻炎症状，例如腹式呼吸和呼吸频率降低，表明鼻塞。15-HEDE 通过激活 K _V引起血管舒张通道和血管通透性增加，这可能导致鼻塞。此外，15-HEDE 可能是一种新的脂质介质，可加剧 AR 中的鼻塞。