Effects of ozone on lung mechanics and cyclooxygenase metabolites in dogs

Abstract

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 (R 1) and dynamic compliance (C dyn) 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 R L 50% (PD 50) and analyzed the BAL for four cyclooxygenase metabolites of AA: a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin F 1α (6-keto-PgF 1α); prostaglandin E 2 (PgE 2); a stable hydrolysis product of thromboxane A 2, thromboxane B 2 (TxB 2); and prostaglandin F 2α (PgF 2α). Following ozone exposure, R L increased from 4.75 +/- 1.06 to 6.08 +/- 1.3 cmH 2O/L/sec (SEM) (p < 0.05), C dyn decraesed from 0.0348 +/- 0.0109 to .0217 +/- .0101 L/cmH 2O (p < 0.05), and PD 50 decreased from 4.32 +/- 2.41 to 0.81 +/- 0.49 mg/cc (p<0.05). The baseline metabolite levels were as follows: 6-keto PgF 1α: 96.1 +/- 28.8 pg/ml; PgE 2: 395.8 +/- 67.1 pg/ml; TxB 2: 48.5 +/- 11.1 pg/ml; PgF 2α: 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.