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Inhibition by thromboxane antagonists of airway hyperresponsiveness to histamine induced by 13,14‐dihydro‐15‐keto‐PGF 2α in guinea‐pigs
Author(s) -
KUROSAWA M.,
YODONAWA S.,
INAMURA H.,
TSUKAGOSHI H.
Publication year - 1994
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.1365-2222.1994.tb00971.x
Subject(s) - histamine , prostaglandin d2 , medicine , airway , bronchial hyperresponsiveness , guinea pig , airway resistance , thromboxane a2 , thromboxane , prostaglandin , compound 48/80 , methacholine , lung , anesthesia , pharmacology , endocrinology , respiratory disease , receptor , platelet , degranulation
Summary. We studied the effect of intravenous administration of 13,14‐dihydro‐15‐keto‐prostaglandin (PG) F 27alpha; on airway 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 section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, 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 13,14‐dihydro‐l5‐keto‐PGF 2n . Intravenous administration of 10/μg/kg 13,14‐dihydro‐15‐keto‐PGF 2α for 1 h did not induce an increase of the relative thickness of the airway wall by the histological examination. In analysis of airway function, intravenous administration of 10μg/kg 13,14‐dihydro‐15‐keto‐PGF 2α for 1 h induced airway hyperresponsiveness to histamine without airway wall thickening. Thromboxane A 2 (TXA 2 ) receptor antagonists ONO‐NT‐126 and ONO‐8809 inhibited the 13,14‐dihydro‐15‐keto‐PGF 2α ‐induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14‐dihydro‐15‐keto‐PGF 2α on bronchial hyperresponsiveness is likely to be mediated through TXA 2 .