Edema from cyclooxygenase products of endogenous arachidonic acid in isolated lung.
We infused A23187, a calcium ionophore, into the pulmonary circulation of dextran-salt-perfused isolated rabbit lungs to release endogenous arachidonic acid. This led to elevations in pulmonary arterial pressure and to pulmonary edema as measured by extravascular wet-to-dry weight ratios. The increase in pressure and edema was prevented by indomethacin, a cyclooxygenase enzyme inhibitor, and by 1-benzylimidazole, a selective inhibitor of thromboxane (Tx) A2 synthesis. Transvascular flux of 125I-albumin from vascular to extravascular spaces of the lung was not elevated by A23187 but was elevated by infusion of oleic acid, an agent known to produce permeability pulmonary edema. We confirmed that A23187 leads to elevations in cyclooxygenase products and that indomethacin and 1-benzylimidazole inhibit synthesis of all cyclooxygenase products and TxA2, respectively, by measuring perfusate levels of prostaglandin (PG) I2 as 6-ketoprostaglandin F1 alpha, PGE2, and PGF2 alpha and TxA2 as TxB2. We conclude that release of endogenous pulmonary arachidonic acid can lead to pulmonary edema from conversion of such arachidonic acid to cyclooxygenase products, most notably TxA2. This edema was most likely from a net hydrostatic accumulation of extravascular lung water with an unchanged permeability of the vascular space, since an index of permeability-surface area product (i.e., transvascular albumin flux) was not increased.
Littner
M R
MR
Department of Medicine, Sepulveda Veterans Administration Medical Center 91343.
Lott
F D
FD
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism; D007213:Indomethacin / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D009929:Organ Size; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000032:analysis; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000209:etiology*; D011669:Pulmonary Wedge Pressure; D011817:Rabbits; D011863:Radioimmunoassay; D013997:Time Factors
D001095:Arachidonic Acids; D007093:Imidazoles; D011453:Prostaglandins; D000001:Calcimycin; C017062:1-benzylimidazole; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin