title: Oxidant- and lipid-induced pulmonary vasoconstriction mediated by arachidonic acid metabolites.
abstract: In experiments using isolated rabbit lungs perfused with Krebs-Henseleit buffer in a nonrecirculating manner, we found that administration of an organic peroxide, tert-butyl hydroperoxide (t-bu-OOH), or Intralipid, an esterified mixture of unsaturated fatty acids, caused a marked vasopressor response which was associated with increased levels of thromboxane in the effluent perfusate. The vasopressor response to t-bu-OOH was greater in the lungs of vitamin E-deficient animals, and this could be correlated with an attenuated ability to increase prostacyclin production in these lungs. Conversely, administration of Intralipid to normal lungs caused marked increases in prostacyclin and a smaller pressor response. The magnitude of the pressor response was strongly correlated with the ratio of thromboxane B2 to the prostacyclin metabolite. No release of these mediators was associated with pulmonary vasoconstriction caused by administration of angiotensin II. The pressor response could be completely blocked by administration of indomethacin. We propose that this activation of the cyclooxygenase pathway of arachidonic acid metabolism may be important in the pathophysiology of oxidant lung damage.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D013929:Thromboxane B2 / Q000032:analysis; D014661:Vasoconstriction / Q000187:drug effects*; D014811:Vitamin E Deficiency / Q000378:metabolism; D020122:tert-Butylhydroperoxide
chemical_list: D001095:Arachidonic Acids; D005217:Fat Emulsions, Intravenous; D010545:Peroxides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D020122:tert-Butylhydroperoxide