Indomethacin and cromolyn sodium alter ozone-induced changes in lung function and plasma eicosanoid concentrations in guinea pigs

Abstract

Male Hartley guinea pigs were given either indomethacin (IN), cromolyn sodium (CS), or no drug (ND) and then exposed either to filtered air or to 1 ppm ozone (O 3) for 1 hr. At 2 or 24 hr postexposure, ventilation, respiratory mechanics, lung volumes, carbon monoxide-diffusing capacity (DL CO), and alveolar volume (VA) were measured, and in separate groups of animals, plasma eicosanoids (EC) were measured. Both drugs blocked the increase in flow resistance noted at 2 hr after O 3 and prevented O 3-induced increases in the wet lung weight to body weight ratio seen at 2 and 24 hr in the ND group. In the ND animals O 3 also decreased total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and residual volume (RV). IN as well as CS blocked reductions in FRC and RV at both 2 and 24 hr after O 3. TLC was reduced by both drug treatments in air- and O 3-exposed animals. CS treatment also decreased VC in all groups. IN blocked reductions in VA after O 3 but did not prevent decreases in DL CO. CS blocked reductions in both VA and DL CO after O 3, but the drug decreased DL CO in air-exposed animals. The prostaglandins PGF 2α and 6-keto PGF 1α were largely unaffected by O 3 exposure or drug treatment. Prostaglandin E 1 (PGE 1) was not affected by O 3, but both drugs significantly increased PGE 1 in all exposure groups. Effects on plasma thromboxane B 2 (TxB 2) were variable although in most groups TxB 2 was lower than in the O 3-exposed ND groups. Although our findings suggest that both drugs block some effects of O 3 exposure on the lungs and on plasma EC concentrations, the degree to which EC contribute to O 3-induced pulmonary effects is not clearly apparent.