[Bronchial hyperresponsiveness to histamine induced by intravenous administration of 13,14-dihydro-15-keto-prostaglandin F2 alpha in guinea pigs].
Prostaglandin F2 alpha (PGF2 alpha) has been suggested to play a role in the pathogenesis of bronchial asthma. In this study, the effects of intravenous administration of 13,14-dihydro-15-keto-PGF2 alpha, a stable metabolite of PGF2 alpha, on bronchial smooth muscle in guinea pigs were investigated by measuring dynamic respiratory resistance using a formula that excludes the effects of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of 13,14-dihydro-15-keto-PGF2 alpha did not induce airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of 13,14-dihydro-15-keto-PGF2 alpha. Moreover, TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the effect of 13,14-dihydro-15-keto-PGF2 alpha administration. These results suggest that 13,14-dihydro-15-keto-PGF2 alpha can be important mediators affecting bronchial hyperresponsiveness, and TXA2 may play a part in the 13,14-dihydro-15-keto-PGF2 alpha-induced bronchial hyperresponsiveness.
Yodonawa
S
S
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kurosawa
M
M
D000284:Administration, Oral; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy; D016084:Bronchoconstriction / Q000187:drug effects; D015237:Dinoprost / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
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