Role of neurogenic inflammation in antigen-induced vascular extravasation in guinea pig trachea.
Conflicting results have been reported about the role of sensory nerves in the allergen-induced plasma extravasation in sensitized guinea pigs using capsaicin desensitization. To investigate the role of tachykinins released from sensory nerves in the anaphylactic reaction in guinea pigs in vivo, we used a selective inhibitor of neutral endopeptidase, phosphoramidon, and a selective neurokinin (NK)-1 receptor antagonist, CP-96,345. Male Hartley guinea pigs were sensitized to OVA by two i.p. injections (70 mg) at 1-wk intervals. Two wk later, the animals were anesthetized and OVA was administered for 2 min by aerosol through a tracheal cannula. Plasma extravasation was assessed by the photometric measurement of the extravasated Evans blue after formamide extraction. Administration of aerosolized OVA to sensitized guinea pigs increased dye extravasation in the trachea in a dose-dependent manner, an effect that was demonstrable 5 min after exposure to allergen and that reached a maximum 10 min after exposure. At 5 min after OVA (5%), phosphoramidon (2.5 mg/kg, i.v.) did not increase the amount of dye in the trachea significantly and CP-96,345 (4 mg/kg) did not decrease the extravasated dye. At 10 min after OVA, allergen-induced plasma extravasation was potentiated by phosphoramidon by 56%, and was inhibited by CP-96,345 (4 mg/kg) by 42%. In the presence of phosphoramidon, CP-96,345 reduced the OVA-evoked plasma extravasation at 10 min in a dose-related manner (0.1-4 mg/kg). CP-96,345 (4 mg/kg) did not affect plasma extravasation induced by platelet-activating factor (100 nmol/kg, i.v.). These results suggest that tachykinin release from sensory nerves after allergen challenge to airways in sensitized guinea pigs is not responsible for the early increase in plasma extravasation, but, tachykinin release appears to play an important role in the subsequent extravasation.
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
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Bertrand
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Geppetti
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Baker
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Yamawaki
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Nadel
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002199:Capillary Permeability; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000494:pharmacology; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014132:Trachea / Q000098:blood supply / Q000276:immunology* / Q000294:innervation
D000941:Antigens; D001713:Biphenyl Compounds; D010972:Platelet Activating Factor; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D010047:Ovalbumin; C066892:CP 96345