[Effects of thromboxane A2 receptor antagonist, KT2-962 on pulmonary hypertensive responses to antigen challenge in isolated sensitized rabbit lung]

Masui. 1995 Jan;44(1):21-5.
[Article in Japanese]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Benzenesulfonates / therapeutic use*
  • Cycloheptanes / therapeutic use*
  • Erythrocytes / immunology
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / immunology
  • In Vitro Techniques
  • Male
  • Perfusion
  • Rabbits
  • Receptors, Thromboxane / antagonists & inhibitors*

Substances

  • Benzenesulfonates
  • Cycloheptanes
  • Receptors, Thromboxane
  • 6-isopropyl-3-(4-(4-chlorobenzenesulfonylamino)butyl)azulene-1-sulfonic acid sodium salt