Inhibition of pulmonary hypertensive response after antigen challenge.
By adding antigen cells into perfusate circulation, a great increase in pulmonary arterial pressure was observed in isolated perfused lung from rabbits previously immunized with human O-N type erythrocytes. To investigate whether thromboxane A2 is the main mediator in pulmonary vasoconstrictive response, we injected antigen erythrocytes into the reservoir after administration of putative inhibition as follows: indomethacin (5 mg/kg, thromboxane A2 synthetase inhibitor), KT2-962 (.1 mg/kg, thromboxane receptor blocker), and pyrilamine (.1 mumol, H1 blocker). Pulmonary vasoconstrictive response after antigen challenge was significantly blocked by both indomethacin and KT2-962, but not by H1 blocker. Although the H1 blocker, pyrilamine, did not significantly block the pulmonary vasoconstrictive response, it did significantly block the bronchoconstrictive response after antigen challenge; however, the bronchoconstrictive response was not blocked by either indomethacin or KT2-962. We conclude that thromboxane is the main mediator in the pulmonary vasoconstrictive response, and histamine is the main mediator in the bronchoconstrictive response.
Enzan
K
K
Department of Emergency Medicine, Akita University School of Medicine, Japan.
Shouji
K
K
Inaba
H
H
Yoshioka
N
N
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D003508:Cycloheptanes / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D006632:Histamine / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology
D000941:Antigens; D001557:Benzenesulfonates; D003508:Cycloheptanes; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D017482:Receptors, Thromboxane; C080458:6-isopropyl-3-(4-(4-chlorobenzenesulfonylamino)butyl)azulene-1-sulfonic acid sodium salt; D013928:Thromboxane A2; D006632:Histamine; D011738:Pyrilamine; D007213:Indomethacin