Regulation of extracellular fluid volume and blood pressure by pendrin.

Na + is commonly designed as the culprit of salt-sensitive hypertension but several studies suggest that abnormal Cl - transport is in fact the triggering mechanism. This review focuses on the regulation of blood pressure (BP) by pendrin, an apical Cl - /HCO 3 - exchanger which mediates HCO 3 secretion and transcellular Cl - transport in type B intercalated cells (B-ICs) of the distal nephron. Studies in mice showed that it is required not only for acid-base regulation but also for BP regulation as pendrin knock-out mice develop hypotension when submitted to NaCl restriction and are resistant to aldosterone-induced hypertension. Pendrin contributes to these processes by two mechanisms. First, pendrin-mediated Cl - transport is coupled with Na + reabsorption by the Na + -dependent Cl - /HCO 3 exchanger NDCBE to mediate NaCl reabsorption in B-ICs. Second, pendrin activity regulates Na + reabsorption by the adjacent principal cells, possibly by interaction with the ATP-mediated paracrine