Cyclooxygenase metabolites contribute to oleic acid-induced lung edema by a pressure effect.
We investigated the role that lung-derived arachidonic acid metabolites play in the acute changes in pulmonary hemodynamics, airway function, and lung fluid balance following oleic acid-induced injury in the isolated blood free perfused lung. A bolus injection of oleic acid (OA) emulsion (12 mg) into the pulmonary artery caused a rapid increase in pulmonary arterial pressure, inspiratory pressure, and weight gain. These pathophysiologic changes were not due to emboli per se, but were correlated with release of the vaso- and broncho-constrictive prostanoids, thromboxane A2 (measured as thromboxane B2) and prostaglandin F2 alpha. The leukotrienes (C4, D4, and E4) and prostacyclin (measured as 6 keto-prostaglandin F1 alpha) were not released by OA injury. Ibuprofen, a cyclooxygenase inhibitor, blocked the release of the vasoconstrictive prostanoids and also attenuated the rise in pressures and the development of edema indicating an important functional role for the prostanoids in the fluid imbalance. Ibuprofen also attenuated the increase in bronchoalveolar lavage protein but the protein leak was not completely prevented, suggesting that OA-induced increases in protein permeability occurred independently of prostanoid or leukotriene action. These data indicate that OA-induced edema formation was greatly amplified by arachidonic acid mediated pressure increases.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D006168:Guinea Pigs; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000633:toxicity*; D011312:Pressure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013189:SRS-A / Q000378:metabolism
D001095:Arachidonic Acids; D009829:Oleic Acids; D011453:Prostaglandins; D013189:SRS-A; D016718:Arachidonic Acid; D019301:Oleic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen