Alveolar fluid clearance (AFC) occurs as the result of active Na transport across the alveolar epithelium where regulation through b-adrenergic stimulation seems to play a central role. We have examined AFC in vivo and the expression of a number of water and electrolyte transporters in a rat model of severe congestive heart failure (CHF). The main finding is that severe CHF is associated with increased, amiloride insensitive AFC. Western blot analyses showed a marked change in the protein levels of the ENaC subunits in whole lung homogenates, with a substantial increase in the a-subunit and marked decrease in the b-subunit when compared to time matched control rats. The protein abundance of CFTR and the a1-subunit of the Na/K-ATPase were unchanged. Finally AQP5 was almost completely absent. Together these findings indicate substantial changes in ENaC function and abundance, which include a shift from highly Na specific amiloride sensitive channels to less specific and less amiloride sensitive channels. Furthermore, the finding that AQP5, expressed in type I, but not type II alveolar cells is almost absent, could suggest alveolar epithelial type II cell proliferation. Studies aimed to further study these hypotheses are currently ongoing.