MODULATION OF LUNG LIQUID CLEARANCE BY ISOPROTERENOL IN RAT LUNGS

beta-Adrenergic agonists have been reported to increase lung Liquid cl earance by stimulating active Na+ transport across the alveolar epithe lium. We studied mechanisms by which beta-adrenergic isoproterenol (Is o) increases lung Liquid clearance in isolated perfused fluid-filled r at lungs. Iso perfused through the pulmonary circulation at concentrat ions of 10(-4) to 10(-8) M increased lung Liquid clearance compared wi th that of control lungs (P < 0.01). The increase in lung liquid clear ance was inhibited by the beta-antagonist propranolol (10(-5) M), the Na+-channel blocker amiloride (10(-4) Mi, and the antagonist of Na-K-A TPase,ouabain (5 x 10(-4) M). Colchicine, which inhibits cell microtub ular transport of ion-transporting proteins to the plasma membrane, bl ocked the stimulatory effects of Iso on active Na+ transport, whereas the isomer lumicolchicine, which does not affect cell microtubular tra nsport, did not inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha(1)-subunit protein abundance and activity incre ased in alveolar type II cells stimulated by 10(-6) M Iso. Colchicine blocked the stimulatory effect of Iso and the recruitment of Na-K-ATPa se alpha(1)-protein to the basolateral membrane of alveolar type II ce lls. Accordingly, Iso increased active Na+ transport and lung liquid c learance by stimulation of beta-adrenergic receptors and probably by u pregulation of apical Na+ channels and basolateral Na-K-ATPase mechani sms. Recruitment from intracellular pools and microtubular transport o f Na+ pumps to the plasma membrane participate in beta-adrenergic stim ulation of lung liquid clearance in rat lungs.