Effects of ozone on cyclooxygenase metabolites in the baboon tracheobronchial tree.
Short-term exposure to 0.5 parts per million (ppm) ozone has been shown to cause an increase in respiratory resistance in primates that can be diminished by 50% with pretreatment with cromolyn sodium. Because of the known membrane-stabilizing effects of cromolyn and the resultant inhibition of mediator production, we hypothesized a role for the products of arachidonic acid (AA) metabolism in these events. We exposed five adult male baboons to 0.5 ppm ozone on two occasions, once with cromolyn pretreatment and once without. Pulmonary resistance (RL) was monitored and bronchoalveolar lavage (BAL) was performed before and after each exposure. The BAL was analyzed for a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin (PG) F1 alpha, PGE2, a stable hydrolysis product of thromboxane (Tx) A2, TxB2, and PGF2 alpha. RL increased after ozone exposure (1.62 +/- 0.23 to 3.77 +/- 0.51 cmH2O.l-1.s, difference 2.15; P less than 0.02), and this effect was partially blocked by cromolyn (1.93 +/- 0.09 to 3.18 +/- 0.40 cmH2O.l-1.s, difference 1.25; P less than 0.02). The base-line levels of the metabolites of AA in the BAL were as follows (in pg/ml): 6-keto-PGF1 alpha 72.78 +/- 12.6, PGE2 145.92 +/- 30.52, TxB2 52.52 +/- 9.56, and PGF2 alpha 22.28 +/- 5.42. Ozone exposure had no effect on the level of any of these prostanoids (P = NS). These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from baboon lungs and demonstrate that changes in the levels of these mediators in BAL are not prerequisites for ozone-induced increases in respiratory resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Fouke
J M
JM
Southwest Foundation for Biomedical Research, San Antonio, Texas 78284.
DeLemos
R A
RA
Dunn
M J
MJ
McFadden
E R
ER
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D008297:Male; D010126:Ozone / Q000633:toxicity*; D010215:Papio; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001095:Arachidonic Acids; D011453:Prostaglandins; D013929:Thromboxane B2; D010126:Ozone; D011451:Prostaglandin-Endoperoxide Synthases