The role of amiloride‐insensitive sodium transport in alveolar fluid homeostasis (695.2)

Abstract

Under both normal and pathological conditions, the lung fluid balance across the alveolar epithelial barrier is mainly regulated by active sodium transporters. Previous work has largely focused on the critical role of ENaC, yet ~60% of alveolar fluid clearance in rats or humans is amiloride insensitive. We decided to explore the role of the amiloride‐insensitive sodium cotransporters SGLT1 (Na+‐glucose co‐transporter 1) and SNATs (Na+‐coupled neutral amino acid transporters) in the intact lung. In isolated perfused rat lungs, we determined alveolar fluid clearance (AFC) using a double indicator dilution technique and probed for the role of SGLT1 and SNATs by addition of appropriate cotransporter substrates or inhibitors. While addition of the SNAT substrate L‐alanine did not affect basal AFC, it rescued AFC in lungs pre‐treated with amiloride, and this response was blocked by the SNAT inhibitor HgCl2. Analysis of bronchoalveolar lavage fluid revealed > 2‐fold of L‐alanine in the epithelial lining fluid compared to plasma level. RT‐PCR identified mRNAs for all 6 SNAT isoforms in whole lung, yet in alveolar epithelial cells, only SNAT 2 and 5 mRNA and protein were detected. In contrast, no functional involvement of SGLT1 in AFC was detected. These results indicate a new role for SNATs in AFC which becomes unmasked when ENaC is inhibited. SNAT2 and SNAT5 may represent novel targets for the resolution of pulmonary edema.Grant Funding Source: Funded by CIHR MOP # 245251