Inhibitory effect of a thromboxane A2 synthetase inhibitor OKY-046 on bronchial hyperresponsiveness to histamine, but not on airway wall thickening, induced by intravenous administration of leukotriene C4 in guinea-pigs.
We studied the effect of i.v.administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea-pigs. The infusion of 3 micrograms/kg LTC4 for 1 h induced an increase of the relative thickness of the airway wall in peripheral bronchi, found by histological examination. In analysis of airway function, the infusion of 3 micrograms/kg LTC4 for 1 h induced airway wall thickening and airway hyperresponsiveness to histamine administered i.v.at doses of 1.8 and 3.6 micrograms/kg. Thromboxane A2 synthetase inhibitor OKY-046, which was administered perorally, inhibited the LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner at doses from 30-100 mg/kg, but not the airway wall thickening induced by LTC4.
Kurosawa
M
M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Tsukagoshi
H
H
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000188:drug therapy*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D017997:Leukotriene C4 / Q000494:pharmacology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D006633:Histamine Antagonists; D008689:Methacrylates; D017997:Leukotriene C4; D006632:Histamine; D013930:Thromboxane-A Synthase; C034364:ozagrel