Hydrophilic solute transport across rat alveolar epithelium

Diffusional fluxes of a series of hydrophilic nonelectrolytes (molecular radii ranging from 0.15 to 0.57 nm) were measured across the alveolocapillary barrier in the isolated perfused fluid-filled rat lung. Radiolabeled solutes were lavaged into the distal air spaces of isolated Ringer-perfused lungs, and apparent permeability-surface area products were calculated from the rates of isotope appearance in the recirculating perfusate. These data were used to estimate theoretical equivalent pore radii in the alveolar epithelium, with the assumption of diffusive flow through water-filled cylindrical pores. The alveolar epithelium is best characterized by two pore populations, with small pores (radius 0.5 nm) occupying 98.7% of total pore area and larger pores (radius 3.4 nm) occupying 1.3% of total pore area. Net water flow out of the alveolar space was measured by including an impermeant solute (dextran) in the lavage fluid and measuring its concentration in the alveolar space as a function of time. Under control conditions, net water flow averaged 167 nl/s. When 24 microM terbutaline was added to the perfusate, net water flow increased significantly to 350 nl/s (P less than 0.001). Terbutaline had no effect on the fluxes of either glycerol (which traverses the small pore pathway) or sucrose (which traverses the large pore pathway). These findings indicate that the intact mammalian alveolar epithelium is complex and highly resistant to the flow of solutes and water.