Alveolar inflammation and arachidonate metabolism in monocrotaline-induced pulmonary hypertension.
We tested the hypothesis that monocrotaline would activate arachidonic acid metabolism in rats. If activation occurred before the pulmonary hypertension developed, arachidonate metabolites could play a role in the hypertensive monocrotaline injury. We found that 1 wk after monocrotaline administration 6-ketoprostaglandin F1 alpha and leukotriene C4 were increased in lung lavages. At 3 wk when pulmonary hypertension was well developed, lung lavage contained increased 6-ketoprostaglandin F1 alpha and thromboxane B2. In addition, the number and activity of white blood cells in the lavages was increased, and abnormal alveolar macrophages were present. The lung extract contained slow-reacting substances including leukotriene D4. Indomethacin administration inhibited the formation of cyclooxygenase metabolites but did not prevent pulmonary hypertension. Diethylcarbamazine administration reduced the numbers and activity of inflammatory cells, increased pulmonary hypertension, prevented right ventricular hypertrophy, and inhibited the formation of slow-reacting substances. We concluded that arachidonate metabolism was activated before pulmonary hypertension developed, that the inflammatory cells in the alveolus accompanied the hypertensive process, and that diethylcarbamazine attenuated both the monocrotaline-induced inflammatory response and the pulmonary hypertension.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001681:Biological Assay; D004049:Diethylcarbamazine / Q000494:pharmacology; D004789:Enzyme Activation; D006168:Guinea Pigs; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000150:complications / Q000201:enzymology; D007213:Indomethacin / Q000494:pharmacology; D007958:Leukocyte Count; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009119:Muscle Contraction / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000150:complications / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000032:analysis; D007507:Therapeutic Irrigation; D013929:Thromboxane B2 / Q000032:analysis; D013997:Time Factors
D001095:Arachidonic Acids; D011763:Pyrrolizidine Alkaloids; D013189:SRS-A; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016686:Monocrotaline; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D004049:Diethylcarbamazine; D007213:Indomethacin