Deficiency of antioxidants has been shown to increase the incidence and severity of ARDS and the propensity for acute edematous lung injury. This study examines the effect of ascorbate (Asc) deficiency on lung epithelial sodium transport. Adult guinea pigs were fed Asc-deficient diet for 7, 14, and 21 days to create mild, moderate, and severe Asc deficiency. The patch-clamp technique was used to study single-channel activity in alveolar type II (AT II) cells. Asc deficiency was confirmed by the significantly lower Asc levels in plasma, lung tissue, and AT-II cells, and by decreased hydroxylation of proline and lysine in Asc-deficient animals. Table 1 shows the effect of Asc deficiency on the probability of finding open sodium channels. There was a two-fold increase in the probability of finding no channel activity in cell-attached apical patches from 14 and 21 days (not 7 days) Asc- deficient animals (Table 1). Addition of Asc to the culture medium and culture of AT-II cells on type IV collagen resulted in partial restoration of channel activity. Table 2 shows patches with no activity in control and 21-day deficient animals. The level of Asc deficiency seen in these animals has been reported in chronic asthmatics, premature infants, and in chronic smokers. We speculate that clinially-relevant levels of Asc deficiency may impair sodium transport mechanisms in the distal lung epithelia resulting in an increased propensity for pulmonary edema.

Table 1 No caption available.
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Table 2 No caption available.
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