Modulation of lung liquid clearance by isoproterenol in rat lungs

Abstract

β-Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na+ transport across the alveolar epithelium. We studied mechanisms by which β-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 β-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 α1-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 α1-protein to the basolateral membrane of alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung liquid clearance by stimulation of β-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 β-adrenergic stimulation of lung liquid clearance in rat lungs.

Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

“…Treatment of rats with insulin increases AFR to a level similar to that we have previously reported for -adrenergic receptor agonists (Saldias et al, 1998;Saldias et al, 2002;Saldias et al, 2000;Sznajder et al, 2002). In some experiments, rats were pretreated with the -receptor antagonist propranolol to prevent a potential increase in AFR due to hypoglycemia-induced catecholamine release.…”

Myosin-Va restrains the trafficking of Na+/K+-ATPase-containing vesicles in alveolar epithelial cells

“…Scale bars: 10m and 4m (magnified images). (Bertorello et al, 1999;Lecuona et al, 2003;Saldias et al, 1998). Recruitment of Na + /K + -ATPase-containing vesicles into the plasma membrane is known to involve both microtubules and the actin network (Bertorello et al, 2003;Bertorello et al, 1999;Saldias et al, 1998).…”

“…In the lungs, the Na + /K + -ATPase located at the basolateral plasma membrane drives the vectorial Na + transport across the alveolar epithelium necessary to keep the alveoli free of edema (Mutlu and Sznajder, 2005;Sznajder et al, 2002). Alveolar fluid reabsorption is increased after stimulation of Na + /K + -ATPase activity by G-protein-coupledreceptor (GPCR) agonists that activate the second messenger cAMP (Frank et al, 2000;Litvan et al, 2006;Saldias et al, 1998). cAMP increases the Na + /K + -ATPase function in alveolar epithelial cells by promoting its recruitment from intracellular vesicle pools into the plasma membrane (Bertorello et al, 1999;Lecuona et al, 2003).…”

Beta1-Adrenergic Agonist Is a Potent Stimulator of Alveolar Fluid Clearance in Hyperoxic Rat Lungs

“…However, inconsistent with rat lungs, b2-adrenergic agonists did not increase alveolar fluid clearance in rabbit and guinea pig lungs (12, 13). Interestingly, isoproterenol increased alveolar fluid clearance via b 1-adrenoceptors in guinea pig lungs (13), whereas isoproterenol increased alveolar fluid clearance via b 2-adrenoceptors in rat lungs (14). Recently, we reported that denopamine, a selective b1-adrenergic agonist, increased alveolar fluid clearance in normal rat and guinea pig lungs (15).…”