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Inhibition of bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C 4 by novel thromboxane A 2 receptor antagonists ONO‐NT‐126 and ONO‐8809 in guinea‐pigs
Author(s) -
KUROSAWA M.,
YODONAWA S.,
TSUKAGOSHI H.
Publication year - 1993
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.1993.tb00262.x
Subject(s) - histamine , leukotriene , medicine , leukotriene c4 , prostaglandin d2 , bronchial hyperresponsiveness , bronchoconstriction , thromboxane a2 , airway , leukotriene d4 , airway resistance , anesthesia , lung , immunology , asthma , prostaglandin , respiratory disease , receptor
Summary We studied the effect of intravenous administration of leukotriene (LT) C 4 on bronchial responsiveness to histamine and airway wall thickening in guinea‐pigs. Guinea‐pigs were killed and the lungs were fixed in formalin. Slides from paraffin‐embedded sections of the lungs were stained and the airways that were cut in transverse sections were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two incides, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline‐Raw and peak‐Raw following intravenous administration of histamine before and after the intravenous administration of LTC 4 . Intravenous administration of 3 μg/kg LTC 4 for 1 hr induced an increase of the relative thickness of the airway wall in peripheral bronchi by the histological examination. In analysis of airway function, intravenous administration of 3 μg/kg LTC 4 for 1 hr induced airway hyperresponsiveness to histamine with airway wall thickening. Thromboxane A 2 receptor antagonists ONO‐NT‐126 and ONO‐8809 inhibited the LTC 4 ‐induced airway hyperresponsiveness to histamine in a dose‐dependent manner, but not the airway wall thickening induced by LTC 4 , suggesting that the effect of LTC 4 on bronchial hyperresponsiveness is likely to be mediated through TXA 2 .