Inhibition by thromboxane antagonists of airway hyperresponsiveness to histamine induced by 13,14-dihydro-15-keto-PGF2 alpha in guinea-pigs.
We studied the effect of intravenous administration of 13,14-dihydro-15-keto-prostaglandin (PG) F2 alpha 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-15-keto-PGF2 alpha. Intravenous administration of 10 micrograms/kg 13,14-dihydro-15-keto-PGF2 alpha 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 10 micrograms/kg 13,14-dihydro-15-keto-PGF2 alpha for 1 h induced airway hyperresponsiveness to histamine without airway wall thickening. Thromboxane A2 (TXA2) receptor antagonists ONO-NT-126 and ONO-8809 inhibited the 13,14-dihydro-15-keto-PGF2 alpha-induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14-dihydro-15-keto-PGF2 alpha on bronchial hyperresponsiveness is likely to be mediated through TXA2.
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
M
M
Kurosawa
S
S
Yodonawa
H
H
Inamura
H
H
Tsukagoshi
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000502:physiology
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; C067427:ONO 8809; C067520:ONO-NT 126; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D013928:Thromboxane A2; D006632:Histamine; D015237:Dinoprost