ALVEOLAR ENDOTOXIN INCREASES ALVEOLAR LIQUID CLEARANCE IN RATS

Under some pathological conditions, ion transport across alveolar epit helial cells is downregulated, whereas under other pathological condit ions, it may be upregulated. Because endotoxin is a biologically relev ant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotox in (220 mu g/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liqu id clearances were studied over 1 h by instillation of a 5% albumin so lution with 1.5 mu Ci of I-125-labeled albumin (6 ml/kg into both lung s). Alveolar liquid clearance was significantly greater at 24 h (36 +/ - 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-ins tilled controls (27 +/- 6%). Although there was an influx of neutrophi ls into the air spaces, there was no increase in lung epithelial perme ability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium c hannel inhibitor, significantly reduced alveolar liquid clearance in t he rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upreg ulates net alveolar fluid clearance in vivo for up to 40 h, a potentia lly important mechanism for accelerating alveolar fluid clearance unde r some pathological conditions. The increase in alveolar Liquid cleara nce 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.