Transepithelial sodium and water transport in the lung. Major player and novel therapeutic target in pulmonary edema.
Active transepithelial transport of sodium from the airspaces to the lung interstitium is a primary mechanism driving alveolar fluid clearance. This mechanism depends on sodium uptake by amiloride-sensitive sodium channels on the apical membrane of alveolar type II cells followed by extrusion of sodium on the basolateral surface by the Na-K-ATPase. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways thus reducing net alveolar fluid reabsorption, and enhancing the extent of alveolar edema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation is short-term and often not sufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with beta-adrenergic agonists and/or epithelial growth factors may induce a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary edema. Similar results have been achieved experimentally by gene transfer enhancing the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary edema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar edema may lead to more effective prevention or treatment for pulmonary edema and acute lung injury.
Sartori
C
C
Department of Internal Medicine and Botnar Center of Clinical Research, CHUV, Lausanne, Switzerland.
Matthay
M A
MA
Scherrer
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U
D000818:Animals; D020346:Aquaporins / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D014867:Water / Q000378:metabolism
D020346:Aquaporins; D015222:Sodium Channels; D014867:Water; D012964:Sodium