Lipopolysaccharide (LPS) increases transepithelial sodium absorption in the guinea‐pig trachea by increasing Na + ,K + ‐ATPase activity

Earlier, we reported that systemic LPS administration increases transepithelial potential difference (V t ) in the guinea‐pig trachea. The increase in V t was abolished by the epithelial sodium channel (ENaC) blocker, amiloride, and inhibited by the prostaglandin synthase inhibitor, indomethacin. Here, we hypothesized that LPS increases Na + absorption by increasing Na + , K + ‐ATPase activity. We investigated the effects of LPS on V t using the isolated, perfused trachea preparation, which allows agents to be added to the luminal or the serosal surface. Eighteen hours after injection with LPS (4 mg/kg, ip), tracheas were removed, mounted on a holder, and perfused with Krebs solution. LPS increased basal V t (‐34.2 ± 6.1 mV) compared to control (‐5.5 ± 1.8 mV, P < 0.05), consistent with increased cation absorption. Subsequently, apical amiloride (10 μM) reduced V t to ‐4.5 ± 2.2 in controls and to ‐13.1 ± 2.9 in LPS‐treated animals indicating increased flux of Na + across the apical membrane. The cation pore‐forming antifungal, amphotericin B (7.5 μM apically) then increased V t to ‐18.9 ± 2.7 in LPS‐treated tracheas compared to ‐7.0 ± 2.1 in controls. V t after apical permeabilization is the result of basolateral ion transport and represents the maximum capacity of Na + , K + ‐ATPase. We conclude that LPS increases Na + absorption, at least in part, via ENaC by increasing the activity of the Na + , K + ‐ATPase. Funded by NIOSH.