Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Vadász, I; Morty, RE; Kohstall, MG; Olschewski, A; Grimminger, F; Seeger, W; Ghofrani, HA.
Oleic acid inhibits alveolar fluid reabsorption: a role in acute respiratory distress syndrome?
AMER J RESPIR CRIT CARE MED 2005 171: 469-479.
Doi: 10.1164/rccm.200407-954OC
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- Co-Autor*innen der Med Uni Graz
- Olschewski Andrea
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Biological Markers - metabolism
- Cell Line - metabolism
- Comparative Study - metabolism
- Disease Models, Animal - metabolism
- In Vitro - metabolism
- Ion Transport - drug effects
- Male - drug effects
- Na(+)-K(+)-Exchanging ATPase - drug effects
- Oleic Acid - toxicity
- Ouabain - pharmacology
- Patch-Clamp Techniques - pharmacology
- Pulmonary Alveoli - drug effects
- Pulmonary Edema - etiology
- Rabbits - etiology
- Reference Values - etiology
- Research Support, Non-U.S. Gov't - etiology
- Respiratory Distress Syndrome, Adult - complications
- Sodium - metabolism
- Water-Electrolyte Balance - drug effects
- Find related publications in this database (Keywords)
- acute lung injury
- alveolar epithelium
- ENaC
- Na+
- K+-ATPase