DIFFERENTIAL-EFFECTS OF SALMETEROL ON LUNG ENDOTHELIAL AND EPITHELIALLEAKAGE IN SHEEP

Salmeterol has been shown to prevent the influx of proteins into the a ir spaces of lungs of guinea pigs given intravenous histamine. To dete rmine whether the salmeterol acts to stabilize the epithelial or endot helial barrier, we ventilated anesthetized sheep with aerosolized salm eterol before infusing histamine intravenously at a rate of 4 mu g . k g(-1) . min(-1) for 3 h. Changes in endothelial permeability were asse ssed by measuring the flow of lymph and proteins from the lungs. The i nflux of proteins into the air spaces was detected by performing singl e-cycle lavages to measure the concentration of circulating I-125-albu min in the epithelial lining fluid. Intravenous histamine increased th e lymph flow to 13.2 +/- 6.8 ml/h compared with the control value of 5 .6 +/- 2.8 ml/h (P < 0.05). Histamine also increased the concentration of I-125-albumin in the epithelial lining fluid from 1.8 +/- 0.9 to 8 .5 +/- 2.5% of the plasma concentration (P < 0.01) and the postmortem lung water volume from 3.5 +/- 0.5 to 5.0 +/- 0.8 mg/g dry lung wt (P < 0.05). Pretreatment with 2.5 mg of aerosolized salmeterol prevented the influx of proteins into the air spaces and the increase in the pos tmortem lung water volume but it also increased the lung lymph flow ev en further to 20.0 +/- 5.6 ml/h (P < 0.05), increased the lymph-to-pla sma protein ratio from 0.77 to 0.91, and tripled the increase in alveo lar-arterial oxygen gradient caused by histamine alone. Pretreatment w ith 2.5 mg of intravenous salmeterol had essentially the same effect a s salmeterol administered by aerosol. We conclude that salmeterol decr eases lung epithelial permeability but increases lung endothelial perm eability due to intravenous histamine in sheep.