Alveolar sodium and liquid transport in mice

Abstract

We have developed a simple isolated lung preparation for measurement of liquid and solute fluxes across mouse alveolar epithelium. Liquid instilled into air spaces was absorbed at the rate ( J w) of 3.7 ± 0.32 ml ⋅ h−1 ⋅ g dry lung wt−1. J w was significantly depressed by ouabain ( P< 0.001) and amiloride ( P < 0.001). Omission of glucose from the instillate or addition of the Na+-glucose cotransport inhibitor phloridzin did not affect J w. However, the low epithelial lining fluid glucose concentration (one-third that of plasma), the larger-than-mannitol permeability of methyl-α-d-glucopyranoside, and the presence of Na+-glucose cotransporter SGLT1 mRNA in mouse lung tissue suggest that there is a Na+-glucose cotransporter in the mouse alveolar-airway barrier. Isoproterenol stimulated J w (6.5 ± 0.45 ml ⋅ h−1 ⋅ g dry lung wt−1; P < 0.001), and this effect was blocked by amiloride, benzamil, ouabain, and the specific β2-adrenergic antagonist ICI-118551 but not by atenolol. Similar stimulation was obtained with terbutaline (6.4 ± 0.46 ml ⋅ h−1 ⋅ g dry lung wt−1). Na+ unidirectional fluxes out of air spaces varied in agreement with J w changes. Thus alveolar liquid absorption in mice follows Na+ transport via the amiloride-sensitive pathway, with little contribution from Na+-glucose cotransport, and is stimulated by β2-adrenergic agonists.