The effect of 15‐HPETE on airway responsiveness and pulmonary cell recruitment in rabbits

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Abstract
In the present study we have investigated the effect of 15‐hydroperoxyeicosatetraenoic acid (15‐HPETE) and 15‐hydroxyeicosatetraenoic acid (15‐HETE) on airway responsiveness to inhaled histamine in rabbits in vivo. 15‐HPETE increased airway responsiveness to histamine 24 h after tracheal instillation and this was associated with a cellular infiltration consisting mainly of neutrophils, as measured by bronchoalveolar lavage. The airway hyperresponsiveness induced by 15‐HPETE was still present 72 h after tracheal instillation of 15‐HPETE, but had returned to baseline values one week post challenge. The number of neutrophils in bronchoalveolar lavage remained significantly elevated compared to pre‐challenge levels. In contrast to 15‐HPETE, the major metabolite 15‐HETE, failed to alter airway hyperresponsiveness to histamine despite the recruitment of neutrophils into the lung, suggesting that the effect of 15‐HPETE was not secondary to the generation of this metabolite nor dependent on the influx of neutrophils. Both capsaicin and atropine but not the peripherally acting μ‐opioid receptor agonist, BW443C (H‐Tyr‐D‐Arg‐Gly‐Phe(4‐NO2)‐Pro‐NH4), attenuated 15‐HPETE‐induced hyperresponsiveness. The increased cellular infiltration induced by 15‐HPETE was only attenuated by capsaicin. The results of the present study suggest that the release of 15‐HPETE into the airways could contribute to sensitization of afferent nerve endings analogous to the hyperalgesia induced by this mediator in skin. British Journal of Pharmacology (1997) 122, 249–256; doi:10.1038/sj.bjp.0701379

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