Thromboxane rather than platelet activating factor mediates pulmonary vasoconstriction after antigen challenge in rabbits.
To investigate whether thromboxane and/or platelet activating factor (PAF) mediate the pulmonary vasoconstrictive response to antigen in vivo, we intra-arterially injected human erythrocytes as antigen into sensitized rabbits after administration of putative inhibitors: a cyclooxygenase synthetase inhibitor (indomethacin, 5 mg.kg-1), a thromboxane synthetase inhibitor (OKY 046, 10 mg.kg-1 + 100 micrograms.kg-1.min-1), and a PAF blocker (CV6209, .1 mg.kg-1). Pulmonary artery and airway pressures significantly increased after the antigen challenge in sensitized rabbits, but did not in nonsensitized rabbits. Both indomethacin and OKY046 significantly inhibited the increase in pulmonary artery pressure after the antigen challenge, while CV6209 did not. CV6209 significantly attenuated the decrease in femoral artery pressure after the antigen challenge, while neither indomethacin nor OKY046 did. There were no significant differences in the increase in airway pressure among the groups. We conclude that thromboxane rather than PAF mediates the pulmonary vasoconstriction after the antigen challenge and that mediators other than thromboxane and PAF mediate bronchoconstriction after the antigen challenge in sensitized rabbits.
Enzan
K
K
Department of Emergency Medicine, Akita University School of Medicine, Japan.
Kurosawa
S
S
Yoshioka
N
N
Inaba
H
H
D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation; D011726:Pyridinium Compounds / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D004791:Enzyme Inhibitors; D008689:Methacrylates; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel; D007213:Indomethacin