Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs.
To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a thromboxane synthase inhibitor (OKY-046, 100 micrograms X kg-1 X min-1 iv) in five dogs exposed to O3. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cmH2O X l-1 X s. O3 (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 (geometric SEM = 1.64) to 0.14 mg/ml (geometric SEM = 1.30). OKY-046 significantly inhibited this effect without altering pre-O3 responsiveness or the O3-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A2, we studied the effect of a thromboxane A2 mimetic, U-46619, on airway responsiveness in five additional dogs. U-46619 in subthreshold doses (i.e., insufficient to increase base-line pulmonary resistance) caused a fourfold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A2 may be an important mediator of O3-induced airway hyperresponsiveness.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004285:Dogs; D008689:Methacrylates / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D013931:Thromboxanes / Q000096:biosynthesis*
D008689:Methacrylates; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D000001:Calcimycin; D010126:Ozone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011451:Prostaglandin-Endoperoxide Synthases; C034364:ozagrel; D000109:Acetylcholine