Effects of ozone on lung mechanics and cyclooxygenase metabolites in dogs.
To determine if acute exposure to ozone can cause changes in the production of cyclooxygenase metabolites of arachidonic acid (AA) in the lung which are associated with changes in lung mechanics, we exposed mongrel dogs to 0.5 ppm ozone for two hours. We measured pulmonary resistance (RL) and dynamic compliance (Cdyn) and obtained methacholine dose response curves and bronchoalveolar lavagate (BAL) before and after the exposures. We calculated the provocative dose of methacholine necessary to increase RL 50% (PD50) and analyzed the BAL for four cyclooxygenase metabolites of AA: a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin F1 alpha (6-keto-PgF1 alpha); prostaglandin E2 (PgE2); a stable hydrolysis product of thromboxane A2, thromboxane B2 (TxB2); and prostaglandin F2 alpha (PgF2 alpha). Following ozone exposure, RL increased from 4.75 +/- 1.06 to 6.08 +/- 1.3 cm H2O/L/sec (SEM) (p less than 0.05), Cdyn decreased from 0.0348 +/- 0.0109 TO .0217 +/- .0101 L/cm H2O (p less than 0.05), and PD50 decreased from 4.32 +/- 2.41 to 0.81 +/- 0.49 mg/cc (p less than 0.05). The baseline metabolite levels were as follows: 6-keto PgF1 alpha: 96.1 +/- 28.8 pg/ml; PgE2: 395.8 +/- 67.1 pg/ml; TxB2: 48.5 +/- 11.1 pg/ml; PgF2 alpha: 101.5 +/- 22.6 pg/ml. Ozone had no effect on any of these prostanoids. These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from dog lungs and demonstrate that changes in their levels are not prerequisites for ozone-induced changes in lung mechanics or airway reactivity.
Fouke
J M
JM
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH.
Wolin
A D
AD
McFadden
E R
ER
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015232:Dinoprostone / Q000096:biosynthesis; D004285:Dogs / Q000502:physiology; D006801:Humans; D008168:Lung / Q000187:drug effects*; D016210:Methacholine Chloride / Q000494:pharmacology; D010126:Ozone / Q000633:toxicity*; D010215:Papio / Q000502:physiology; D011460:Prostaglandins F / Q000096:biosynthesis; D012129:Respiratory Function Tests; D013929:Thromboxane B2 / Q000096:biosynthesis
D011460:Prostaglandins F; D016210:Methacholine Chloride; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010126:Ozone; D015232:Dinoprostone; C100006:prostaglandin F1