The effect of 15-HPETE on airway responsiveness and pulmonary cell recruitment in rabbits.
1. 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. 2. 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. 3. Both capsaicin and atropine but not the peripherally acting mu-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. 4. 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.
Riccio
M M
MM
Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, Kings College School of Medicine and Dentistry, London.
Matsumoto
T
T
Adcock
J J
JJ
Douglas
G J
GJ
Spina
D
D
Page
C P
CP
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002211:Capsaicin / Q000494:pharmacology; D006632:Histamine; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D015289:Leukotrienes / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000294:innervation; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011817:Rabbits
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D018727:Muscarinic Antagonists; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001285:Atropine; D006632:Histamine; D002211:Capsaicin