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Am J Physiol Lung Cell Mol Physiol 274: L694-L701, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 5, L694-L701, May 1998

Modulation of lung liquid clearance by isoproterenol in rat lungs

F. Saldías, E. Lecuona, E. Friedman, M. L. Barnard, K. M. Ridge, and J. I. Sznajder

Division of Pulmonary and Critical Care Medicine, Michael Reese Hospital, University of Illinois at Chicago, Chicago, Illinois 60616; and Departamento de Enfermedades Respiratorias, Pontificia Universidad Católica de Chile, Santiago, Chile

beta -Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na+ transport across the alveolar epithelium. We studied mechanisms by which beta -adrenergic isoproterenol (Iso) increases lung liquid clearance in isolated perfused fluid-filled rat lungs. Iso perfused through the pulmonary circulation at concentrations of 10-4 to 10-8 M increased lung liquid clearance compared with that of control lungs (P < 0.01). The increase in lung liquid clearance was inhibited by the beta -antagonist propranolol (10-5 M), the Na+-channel blocker amiloride (10-4 M), and the antagonist of Na-K-ATPase, ouabain (5 × 10-4 M). Colchicine, which inhibits cell microtubular transport of ion-transporting proteins to the plasma membrane, blocked the stimulatory effects of Iso on active Na+ transport, whereas the isomer lumicolchicine, which does not affect cell microtubular transport, did not inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha 1-subunit protein abundance and activity increased in alveolar type II cells stimulated by 10-6 M Iso. Colchicine blocked the stimulatory effect of Iso and the recruitment of Na-K-ATPase alpha 1-protein to the basolateral membrane of alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung liquid clearance by stimulation of beta -adrenergic receptors and probably by upregulation of apical Na+ channels and basolateral Na-K-ATPase mechanisms. Recruitment from intracellular pools and microtubular transport of Na+ pumps to the plasma membrane participate in beta -adrenergic stimulation of lung liquid clearance in rat lungs.

active sodium transport; lung edema clearance; apical sodium channels; sodium-potassium-adenosinetriphosphatase; cytoskeleton


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