Am. J. Respir. Crit. Care Med., Vol 149, No. 6, 06 1994, 1488-1493.
Involvement of thromboxane A2 in propranolol-induced bronchoconstriction after allergic bronchoconstriction in guinea pigs
N Songur, M Fujimura, K Mizuhashi, M Saito, QY Xiu and T Matsuda
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Although it is well recognized that beta-blockers can induce
bronchoconstriction only in patients with asthma, mechanisms of the
bronchoconstriction are not well known. We hypothesize that
bronchoconstriction induced by beta-blockers may result from inflammatory
mediators released by allergic reactions. In this study, we developed a
guinea pig model for propranolol-induced bronchoconstriction (PIB) after
antigen inhalation and investigated the effect of specific thromboxane
(TXA2) receptor antagonists, S-1452 and ONO NT-126, on PIB in passively
sensitized and artificially ventilated guinea pigs to determine whether
TXA2 is involved in PIB. Propranolol caused bronchoconstriction with 10
mg/ml of propranolol was inhaled 20 min after antigen challenge. On the
other hand, propranolol did not produce bronchoconstriction after antigen
provocation in nonsensitized guinea pigs or after saline provocation in
sensitized animals. Pretreatment of the animals with S-1452 in doses of
0.01 and 0.1 mg/kg and ONO NT-126 in doses of 1.0 and 10 micrograms/kg
injected intravenously 15 min after antigen challenge as well as before
antigen challenge reduced PIB in a dose-dependent manner.
Bronchoconstriction caused by methacholine did not induce PIB. These
results suggest that TXA2 has an important role in the pathophysiology of
the PIB that develops after the allergic bronchoconstriction.
