Indomethacin and cromolyn sodium alter ozone-induced changes in lung function and plasma eicosanoid concentrations in guinea pigs.
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 (O3) for 1 hr. At 2 or 24 hr postexposure, ventilation, respiratory mechanics, lung volumes, carbon monoxide-diffusing capacity (DLCO), 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 O3 and prevented O3-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 O3 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 O3. TLC was reduced by both drug treatments in air- and O3-exposed animals. CS treatment also decreased VC in all groups. IN blocked reductions in VA after O3 but did not prevent decreases in DLCO. CS blocked reductions in both VA and DLCO after O3, but the drug decreased DLCO in air-exposed animals. The prostaglandins PGF2 alpha and 6-keto PGF1 alpha were largely unaffected by O3 exposure or drug treatment. Prostaglandin E1 (PGE1) was not affected by O3, but both drugs significantly increased PGE1 in all exposure groups. Effects on plasma thromboxane B2 (TxB2) were variable although in most groups TxB2 was lower than in the O3-exposed ND groups. Although our findings suggest that both drugs block some effects of O3 exposure on the lungs and on plasma EC concentrations, the degree to which EC contribute to O3-induced pulmonary effects is not clearly apparent.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D011453:Prostaglandins / Q000097:blood*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D013931:Thromboxanes / Q000097:blood*; D014109:Total Lung Capacity
D011453:Prostaglandins; D013931:Thromboxanes; D010126:Ozone; D004205:Cromolyn Sodium; D007213:Indomethacin