Anticholinergic agents prevent guinea-pig airway constriction induced by histamine, bradykinin and leukotriene C 4: Relationship to circulating TXA 2

Abstract

Various doses of histamine, bradykinin and leukotriene C 4 caused bronchoconstriction in anaesthetized guinea-pigs which were breathing spontaneously or artificially ventilated; there was a simultaneous, dose-related increase of circulating TXA 2. The animals were prepared for continuous recording of extracororeal circulation in order to detect the appearance in the blood of bioassayable levels of TXA 2-like substance. Furthermore, a TXA 2 derivative, the mono-O-Me-TXB 2, was radioimmunoassayed. Atropine, oxytropium bromide and ipratropium bromide given in μmol doses prevented both the increased airway resistance and the release of TXA 2-like substance in the blood. Pirenzepine dihydrochloride was the least active of the drugs tested. The protecting activity of anticholinergics and the relationship with their ability to affect TXA 2-like substance generation suggest a new site of action for these drugs besides the blockade of muscarinic receptors.