Attenuating effect of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to methacholine is specific to bronchial asthma.
To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness (BHR) is specific to asthma, we examined the effects of a selective inhibitor of thromboxane synthetase (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in normal subjects and patients with chronic bronchitis, diffuse bronchiectasis, and intrinsic bronchial asthma. The provocative concentration of methacholine producing a 20 percent fall in forced expiratory volume in 1 s (PC20-FEV1) was measured before and after oral administration of OKY-046 (2,600 mg over four days) and indomethacin (450 mg over three days) in ten normal, ten bronchitic, nine bronchiectatic, and eight asthmatic subjects, respectively. Baseline values of FEV1 and forced vital capacity (FVC) were not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in normal, bronchitic, or bronchiectatic subjects. On the other hand, PC20-FEV1 increased significantly (p less than 0.005) from 2.19 to 8.13 mg/ml after indomethacin in bronchiectatic subjects, but not in normal, bronchitic, or asthmatic subjects. We conclude that the involvement of thromboxane A2 in BHR may be specific to asthma, and bronchial responsiveness of bronchiectasis may be potentiated by inflammatory release of bronchoconstrictor prostaglandins except for thromboxane A2. Further studies using thromboxane A2 receptor antagonists are needed to confirm the conclusion.
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
M
M
Fujimura
S
S
Sakamoto
T
T
Matsuda
D000179:Acrylates / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001987:Bronchiectasis / Q000503:physiopathology; D001991:Bronchitis / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D008689:Methacrylates / Q000494:pharmacology*; D008875:Middle Aged; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014797:Vital Capacity
D000179:Acrylates; D008688:Methacholine Compounds; D008689:Methacrylates; D016210:Methacholine Chloride; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel; D007213:Indomethacin