Inhibition of antigen-induced airway hyperresponsiveness by a thromboxane synthetase inhibitor (OKY-046) in allergic dogs.
To determine the role of thromboxane A2 in the airway hyperresponsiveness induced by antigen challenge, we studied the effect of a thromboxane synthetase inhibitor, OKY-046, i.e., sodium (E)-3-[4-(1-imidazolylmethyl)-phenyl]-2-propanoate, in 6 ragweed-sensitized dogs. Airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus total pulmonary resistance before and 6 and 24 h after inhalation with ragweed antigen. This procedure was repeated in each dog during intravenous infusion of OKY-046 (100 micrograms/kg/min). OKY-946 did not alter the acute increase in total pulmonary resistance after antigen. At 6 h, there was a 7-fold increase in airway responsiveness, an effect that was prevented by OKY-046 (p less than 0.001). At 24 h, 18 h after OKY-046 was stopped, hyperresponsiveness was still significantly inhibited. OKY-046 did not alter the influx of neutrophils recovered by bronchoalveolar lavage performed at 6 h after antigen challenge. Antigen-induced airway hyperresponsiveness in dogs may depend upon the thromboxane A2 generation from inflammatory cells (e.g., neutrophils).
D000179:Acrylates / Q000627:therapeutic use*; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D004285:Dogs; D006967:Hypersensitivity / Q000188:drug therapy*; D008689:Methacrylates / Q000627:therapeutic use*; D011058:Pollen; D012137:Respiratory System / Q000187:drug effects*; D007507:Therapeutic Irrigation; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000179:Acrylates; D000336:Aerosols; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel