Role and regulation of lung Na,K-ATPase.
The recognition that pulmonary edema is cleared from the alveolar airspace by active Na+ transport has led to studies of the role and regulation of alveolar epithelial Na,K-ATPases. In the lung these heterodimers are predominantly composed of alpha1 and beta1-subunits and are located on the basolateral aspect of alveolar type 2 epithelial cells (AT2). Working with apically positioned epithelial Na+ channels they generate a transepithelial osmotic gradient which causes the movement of fluid out of the alveolar airspace. Accumulating data indicates that in some forms of pulmonary edema alveolar Na,K-ATPases function is reduced suggesting that pulmonary edema may be due, in part, to impairment of edema clearance mechanisms. Other studies suggest that Na,K-ATPase dysfunction or inhibition may contribute to airway reactivity. It is now recognized that lung Na,K-ATPases are positively regulated by glucocorticoids, aldosterone, catecholamines and growth hormones. These findings have led to investigations that show that enhancement of Na,K-ATPase function can accelerate pulmonary edema clearance in vitro, in normal and injured animal lungs in vivo, and in human lung explants. This review focuses on Na,K-ATPase data from lung and lung cell experiments that highlight the importance of Na,K-ATPases in airway reactivity and in maintaining a dry alveolar airspace. Review of data that suggests that there may be a role for therapeutic modulation of alveolar Na,K-ATPases for the purpose of treating patients with respiratory failure are also included.
Factor
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P
Pulmonary and Critical Care Medicine, Evanston Northwestern Healthcare, IL 60201, USA. pfactor@northwestern.edu
D000818:Animals; D001980:Bronchi / Q000201:enzymology*; D002395:Catecholamines / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000201:enzymology* / Q000503:physiopathology; D008954:Models, Biological; D010100:Oxygen / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D011654:Pulmonary Edema / Q000201:enzymology / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D002395:Catecholamines; D006728:Hormones; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen