[Effects of thromboxane A2 receptor antagonist, KT2-962 on pulmonary hypertensive responses to antigen challenge in isolated sensitized rabbit lung].
We investigated whether KT2-962 (thromboxane H2/A2 receptor antagonist) could attenuate increases in pulmonary arterial and airway pressures after antigen challenge in isolated-perfused sensitized rabbit lungs. Sensitized rabbits were immunized intravenously with human O-N type erythrocytes until the agglutination titer against antigen reached above 1:10,000. Nineteen rabbits were divided into three groups. In N group (n = 9), antigen was challenged into perfusate. In KT2 group (n = 5), 1 mg.kg-1 of KT2-962 was given into reservoir 10 min prior to antigen challenge. In Indo group (n = 5), 5 mg.kg-1 of indomethacin was given into reservoir 20 min prior to antigen challenge. Maximal increase in pulmonary arterial pressure after antigen challenge in N group was significantly higher than that in KT2 group or in Indo group (13.4 +/- 3.3 mmHg, 1.5 +/- 0.5mmHg, 1.5 +/- 0.2mmHg, respectively). Maximal increase in airway pressure in N group was higher than that in KT2 group or in Indo group (2.9 +/- 0.8cmH2O, 0.8 +/- 0.2cmH2O, 0.5 +/- 0.2cmH2O, respectively), but this was not significant. Pharmacological potential of KT2-962 to attenuate pulmonary hypertensive responses was estimated 50 times stronger than that of indomethacin. In conclusion, KT2-962 can exert therapeutic effect on pulmonary hypertensive responses induced by immunological reactions.
Shoji
K
K
Department of Anesthesiology, Akita University School of Medicine.
Enzan
K
K
Masaki
Y
Y
Suzuki
M
M
Yoshioka
N
N
D000818:Animals; D001557:Benzenesulfonates / Q000627:therapeutic use*; D003508:Cycloheptanes / Q000627:therapeutic use*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*
D001557:Benzenesulfonates; D003508:Cycloheptanes; D017482:Receptors, Thromboxane; C080458:6-isopropyl-3-(4-(4-chlorobenzenesulfonylamino)butyl)azulene-1-sulfonic acid sodium salt