Influence of SK&F 96148 on thromboxane-mediated responses in the airways of the cat.
The effects of SK&F 96148, a thromboxane receptor blocking agent, on bronchoconstrictor responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. I.v. injections of the thromboxane A2 (TXA2) mimics, U-46619 and U-44069, produced dose-related increases in transpulmonary pressure and lung resistance (RL) and decreases in dynamic compliance (Cdyn). After administration of SK&F 96148, 5 mg/kg i.v., bronchoconstrictor responses to U-46619 and U-44069 were reduced markedly, whereas airway responses to prostaglandin (PG) F2 alpha, serotonin, PGD2, or the PGD2 metabolite, 9 alpha, 11 beta-PGF2, were not altered. The duration of action of SK&F 96148 was greater than 2 h, and the TXA2 receptor blockade was overcome when 10-fold larger doses of the TXA2 mimics were administered. Bronchoconstrictor responses to arachidonic acid, platelet-activating factor (PAF), endothelin-1, and E. coli endotoxin were blocked by SK&F 96148. The present data suggest that SK&F 96148 has selective thromboxane receptor blocking activity in the airways of the cat, and that bronchoconstrictor responses to endothelin-1, arachidonic acid, PAF, and E. coli endotoxin are mediated in part by the formation of TXA2.
Dyson
M C
MC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002415:Cats; D016232:Endothelins / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000502:physiology*
D001095:Arachidonic Acids; D016232:Endothelins; D004731:Endotoxins; D010648:Phenylacetates; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D013931:Thromboxanes; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C051762:daltroban