Significance of active ion transport in transalveolar water absorption: a study on isolated rat lung.

1. Experiments were performed on isolated rat lungs perfused with Ringer solutions containing red cells. The goal was to clarify the role of active transport of Na+ for the absorption of fluid across the alveolar membrane, and to characterize active and passive pathways. 2. Partially degassed lungs were filled with 5 ml of an isotonic Ringer solution containing 125I-labelled albumin in order to calculate the fluid movement, and 22Na+ or 36Cl- for measurement of ion fluxes. Passive non-electrolyte permeability was determined in all experiments using [3H]mannitol. 3. The average rate of fluid absorption in phosphate-buffered instillates was 134 nl/s (S.E., 18.5; n = 14). With ouabain (10(-4) M) in the perfusate the fluid absorption rate fell to 57 nl/s (S.E., 8.2; n = 18). Amiloride (10(-3)-10(-4) M) in the instillate reduced the absorption to 75 nl/s (S.E., 8.6; n = 16). These results show that fluid absorption depends on transcellular transport of Na+ and that alveolar epithelial cells have a Na+ entry system in the luminal membrane and a Na+-K+ pump in the abluminal membrane. 4. The transcellular ion transport operates in parallel with a paracellular, passive leak that allows mannitol to pass with a permeability surface area product of 1.2 X 10(-4) ml/s, corresponding to a permeability coefficient of 2.4 X 10(-8) cm/s, assuming an alveolar surface area of 5000 cm2. 5. The passive fluxes of Na+ were 9.4 pmol/(cm2s) (S.E., 1.3; n = 25) in the direction from alveoli to perfusate and 8.0 pmol/(cm2s) (S.E., 0.86; n = 6) from perfusate to plasma. The passive fluxes of Cl- in the two directions were not significantly different either. Thus the transalveolar electrical potential difference is too small to affect ion movements measurably. 6. The passive permeability to Na+ was 6.7 X 10(-8) cm/s and to Cl- was 10.2 X 10(-8) cm/s (alveolar surface area assumed to be 5000 cm2). The ratio of the permeabilities is close to the ratio of the diffusion coefficients in free solution, suggesting a neutral or weakly charged paracellular channel. 7. We conclude that the alveolar epithelium performs solute-coupled fluid transport from alveoli to plasma, and that it shows many features that are common to other fluid-transporting epithelia; with an approximate surface area of 100 m2 in humans it constitutes one of the largest epithelial surfaces in the body.(ABSTRACT TRUNCATED AT 400 WORDS)