Effect of an inhaled thromboxane mimetic (U46619) on in vivo pulmonary resistance and airway hyperresponsiveness in dogs.
1. We investigated the role of thromboxane A2 in the airway hyperresponsiveness that follows the inhalation of ozone in dogs by examining the responses to an inhaled thromboxane analogue (U46619). 2. Measurements of pulmonary resistance were made in anaesthetized dogs; the concentration of inhaled agonist causing an increase of 5 cmH2O l-1 s was calculated (provocative concentration). The effect of inhaled U46619 was studied on in vivo canine airway resistance, on airway responsiveness and on airways made hyperresponsive following the inhalation of ozone. 3. Inhaled thromboxane is a potent constrictor of the canine airway. The mean provocative concentration was 2.13 x 10(-4) M, compared to acetylcholine which was 3.23 x 10(-2) M. 4. Inhaled thromboxane did not result in the development of airway hyperresponsiveness to acetylcholine. Following U46619 inhalation the mean provocative concentration to acetylcholine was 3.92 x 10(-2) M. 5. Canine airway was not hyperresponsive to inhaled thromboxane following the inhalation of ozone. This was not due to an inhibition of acetylcholinesterase as the dogs were hyperresponsive to carbachol (a muscarinic agonist not degraded by endplate cholinesterase). 6. These experiments do not support a role for thromboxane in the development of airway hyperresponsiveness following the inhalation of ozone in dogs.
Jones
G L
GL
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Lane
C
C
O'Byrne
P M
PM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D010126:Ozone / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D010126:Ozone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine