Oleic acid inhibits alveolar fluid reabsorption: a role in acute respiratory distress syndrome?
Levels of oleic acid (OA) are elevated in plasma and bronchoalveolar lavage fluids of patients with acute respiratory distress syndrome (ARDS). OA is also widely used to provoke edema, by unknown mechanisms, in experimental models of ARDS. We investigated the impact of intravascularly applied OA on epithelial lining fluid balance. OA (25 microM) dramatically blocked active transepithelial (22)Na(+) transport (by 92%) in an isolated, ventilated, and perfused rabbit lung model, provoking alveolar edema, assessed by increases in lung weight and epithelial lining fluid volume. OA did not alter epithelial permeability, measured by [(3)H]mannitol and fluorescently labeled albumin flux, but did increase endothelial permeability, assessed by capillary filtration coefficient. In A549 cells, OA completely blocked amiloride-sensitive sodium currents measured by patch clamp, and also largely abrogated ouabain-sensitive Na(+),K(+)-ATPase-mediated (86)Rb(+) uptake. Although OA did not alter epithelial sodium channel or Na(+),K(+)-ATPase surface expression, it covalently associated with both molecules and directly, dramatically, and dose-dependently inhibited the catalytic activity of purified Na(+),K(+)-ATPase. Therefore, OA impaired the two essential transepithelial active sodium transport mechanisms of the lung, and could thus promote alveolar edema formation and prevent edema resolution, thereby contributing to the development of ARDS.
Vadász
István
I
University of Giessen Lung Center, Justus Liebig University, Klinikstrasse 36, D-35392 Giessen, Germany.
Morty
Rory E
RE
Kohstall
Markus G
MG
Olschewski
Andrea
A
Grimminger
Friedrich
F
Seeger
Werner
W
Ghofrani
Hossein A
HA
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D019301:Oleic Acid / Q000633:toxicity*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism*; D011817:Rabbits; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D015415:Biomarkers; D019301:Oleic Acid; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase