cAMP and beta-adrenergic stimulation of rat alveolar epithelium. Effects on fluid absorption and paracellular permeability.

The absorption of fluid (bicarbonate-buffered Ringer with 10 mmol/l glucose) instilled into rat lungs is a Na+-coupled process that takes place through two apical transport systems: an amiloride-sensitive Na+ transport and a Na+-glucose co-transport. Fluid absorption in isolated, perfused rat lungs and the permeability to 3H-mannitol of alveolar epithelium were studied in control conditions and during stimulation of the alveolar epithelium by cAMP or isoproterenol. cAMP led to a threefold increase in the rate of fluid absorption and to an increase in the paracellular permeability. A similar response was found following beta-adrenergic stimulation obtained with isoproterenol in the perfusate. The increase in fluid transport was due to enhancement of the amiloride-sensitive component of Na+ transport. The Na+-glucose co-transport which accounts for about 60% of fluid absorption in control conditions was depressed, possibly as a consequence of a depolarization of the apical alveolar cell membrane. Fluid absorption was reduced by 40% by apical amiloride (10(-4) mol/l) in control lungs and to an even larger extent in isoproterenol-stimulated lungs; it was completely abolished by amiloride in cAMP stimulated lungs. Since the Na+-glucose co-transport was still operative, this suggests that a secretory process was triggered. This was confirmed in experiments in which both kinds of transport were inhibited with a combination of amiloride and glucose-free Ringer. In these conditions fluid balance was zero in unstimulated lungs whilst fluid entry into alveoli was observed in isoproterenol and cAMP stimulated lungs.