ET-1 induced bronchoconstriction in the early phase but not late phase of anesthetized dogs is inhibited by indomethacin and ICI 198615.
Intratracheally injected or aerosolized ET-1 induced quick and long-lasting bronchoconstriction of anesthetized mongrel dogs, thus increasing respiratory resistance(Rrs) with concomitantly decreasing dynamic compliance(Cdyn). As collateral resistance(Rcs) was measured postexposure to aerosolized ET-1 using wedged bronchoscope technique, ET-1 increased Rcs in a dose and time dependent manner. The increase attained maximal in 2 min and then, gradually declined. When the dogs were pretreated with the intravenous injection of 0.1 micrograms/kg ICI 198615, an inhibitor of lipoxygenase, the constrictive response was slowed down. Essentially similar results were also observed with the intravenous injection of 5 mg/kg indomethacin. Our observations suggest that the early phase of the ET-1 induced bronchoconstriction is mediated by eicosanoid metabolites.
Uchida
Y
Y
Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan 48202.
Hamada
M
M
Kameyama
M
M
Ohse
H
H
Nomura
A
A
Hasegawa
S
S
Hirata
F
F
D000771:Anesthesia, Intravenous; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors
D016232:Endothelins; D007191:Indazoles; D013189:SRS-A; C054217:ICI 198615; D007213:Indomethacin