Upregulation of alveolar epithelial fluid transport after subacute lung injury in rats from bleomycin

Abstract

Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). An isosmolar Ringer lactate solution with 5% bovine serum albumin and125I-labeled albumin as the alveolar protein tracer was instilled into the right lung; the rats were then studied for either 1 or 4 h. Alveolar fluid clearance was increased in bleomycin-injured rats by 110% over 1 h and by 75% over 4 h compared with control rats ( P < 0.05). The increase in alveolar fluid clearance was partially inhibited by amiloride (10−3 M). Alveolar fluid clearance decreased toward normal levels in rats that were studied 60 days after bleomycin instillation. Remarkably, the measured increase in net alveolar fluid clearance occurred in the presence of a significant increase in alveolar epithelial permeability to protein. Moreover, the increase in alveolar epithelial fluid clearance occurred even though the mRNA for the α-subunit of the epithelial sodium channel was decreased in alveolar epithelial type II cells isolated from these rats. In addition,22Na uptake by isolated alveolar epithelial type II cells from rats treated with bleomycin demonstrated a 52% decrease in uptake compared with type II cells from control rats. Morphological results demonstrated a significant hyperplasia of alveolar type II epithelial cells 10 days after bleomycin injury. Thus, these results provide evidence that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the transport capacity of the alveolar epithelium, even though the expression of epithelial sodium channels is reduced and the uptake of22Na per cell is also reduced. These results may have clinical relevance for the resolution of alveolar edema in the subacute phase of lung injury.

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema

“…Consequently, the ex vivo measurements of lung liquid clearance were made 7 days after gene transfer, under conditions of ongoing epithelial barrier dysfunction characterised by generalised epithelial permeability to both sodium and mannitol. This 7-day time-point corresponds more closely to the 'subacute' phase of resolution of alveolar epithelial injury, 28 characterised by proliferation of alveolar type II cells. The potential clinical use…”

Regulation of prostasin by aldosterone in the kidney

“…The activities of ENaC in M-1 cells were determined by measurement of amiloride-sensitive 22 Na uptake (16). Preliminary experiments determined that amiloride-sensitive uptake of 22 Na was linear for up to 15 minutes.…”

Alveolar Epithelial β2-Adrenergic Receptors

“…As such, it is unclear whether b 2 ARmediated up-regulation of active Na 1 transport is possible during severe lung injury. Some experimental ALI models (i.e., prolonged hemorrhagic shock, hyperoxia, ischemia reperfusion after lung transplantation, and ventilator-induced lung injury) have been linked with diminished b-receptor function (111)(112)(113)(114)(115)(116). Recently, Davis and coworkers have reported decreased sensitivity to b-agonists in a murine model of respiratory syncytial virus infection (83).…”