Indomethacin potentiates the pulmonary response to aerosol leukotriene C4 in the guinea pig.
Aerosol administration of leukotriene (LT) C4 to anesthetized, mechanically ventilated guinea pigs results in significant dose-dependent decrements in dynamic compliance (Cdyn) and pulmonary conductance (GL) when the concentration of LTC4 in the nebulizer is in the range of 0.5 to 5 micrograms/ml. Pretreatment with indomethacin, 30 mg/kg given intraperitoneally, significantly potentiates the decrements in Cdyn and GL elicited by aerosol LTC4 at 1 microgram/ml. Potentiation of the pulmonary response is seen even with an aerosol LTC4 concentration of 0.3 micrograms/ml, which alone produces only minimal changes in pulmonary mechanics in control animals. These findings suggest that bronchodilator prostaglandins are important inhibitory modulators of this pulmonary response and that secondary thromboxane release probably does not contribute to the response to inhaled LTC4. The effect of indomethacin pretreatment in augmenting the pulmonary response to aerosol LTC4 in the guinea pig may have relevance for the phenomenon of asthma induced in humans by ingestion of nonsteroidal anti-inflammatory agents.
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000139:chemically induced; D001980:Bronchi / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology*; D013931:Thromboxanes / Q000502:physiology
D000336:Aerosols; D011453:Prostaglandins; D013189:SRS-A; D013931:Thromboxanes; D007213:Indomethacin